Multinodular Goiter

Multinodular Goiter - Euthyroid Patient : 

Non-Tender-thyroid nodule.

USG: 

Asthma Severity and Treatment

Asthma management

mnemonic of Eosinophilia

mnemonic of Eosinophilia

Patient Safety WHO

THE PATIENT SAFETY FRIENDLY HOSPITAL INITIATIVE INTRODUCTION

Patient safety : Patient safety is a global health concern as it affects patient in all health care settings whether developed or developing.
Various research studies have shown that an estimated average of 10 percent of all inpatient admission result in a degree of unintended patient harm.
It is estimated that up to 75 percent of these cases in health care delivery can be preventable.

What is Patient safety friendly hospital initiative ?

The initiative involves the implementation of a set of patient safety standards in hospitals.
Abidance by such standards ensures that patient safety is of it most priority and is observed by facilities of staff for achievement of best practices.
The initiative has been pilot tested in 7 countries of the region ( Egypt , Jordon, Morocco,Pakistan , Sudan , Tunisia, Yemen) and experts have been trained to conduct assessment.

What is the purpose of Patient Safety standard ?

Patient Safety standard will provide a frame work for hospitals.

• It will deliver safer patient care by assessing hospitals.
• It will help to build capacity of staff regarding patient safety and involving consumers in improving health care safety.

What is Patient Safety Friendly Hospital Assessment and what are its benefits?

its a mechanism developed to assess patient safety hospitals. The assessment is conducted through an external measurement based evolution. It is voluntary for the moment WHO/EMRO regional Adviser Group on patient safety is the primary assessment team for PSFHA.
The benefits if PSFHA include the hospitals would demonstrate their commitment and accountability regarding patient safety to the public.

What is the not of WHO in supporting of Patient Safety Hospital Initiative ?

PSFHI is a WHO initiative arrived at assembling institutions with in countries to launch a comprehensive patient safety program.
Ultimately it is hoped that this initiative will be owned by the institutions and ministries of health.

What are the patient safety standards and how are they organized ?

Patient safety standards are a set of requirement that are critical for the establishment of a patient program at hospital level.
They are organized under five domains each domains in formed of a number of standards.
There are 24 sub domains and for each sub domains a set of standards is utilized to determine complain with the standards.

• Triage Centre
• Chanel of Communications
• hand hygiene 
• Concert before any procedure
• Decontamination of the instruments
• Comments registrars

SOP Standard operating procedure.

Case: Left Renal Calculus (Renal Stones)

H/O left pyelolithiasis 17 year

H/O Right Nephrectomy 14 year with Tubular Pyonephrosis

B.P 140/85

USG :

shows Mild dilatation of all Calyces of Left Kidney with 1.1 cm echogenic shadow -> Lower calyx.

Liver, Gallbladder, Bile ducts, Spleen and Urinary Bladder are normal .

Right Kidney is absent .

Case 1 :Mild Hydronephrosis with Proximal hydroureter

Dengue fever and its prevention

Breakbone fever mosquito borne tropical disease ''Dengue Virus''

Symptoms :-

Febrile phase

• Sudden onset fever
• headache
• mouth and nose bleeding
• muscle and joint pains
• Vomiting
• rash
• diarrhea

Critical phase

• Hypotension
• pleural effusion
• ascites
• GI bleeding 

Recovery phase

• Altered level of consciousness
• seizures
• itching
• slow heart rate

Common symptoms :

1.Fever
2.Headache
3.Muscular and joint pain
4.Skin rash similar to measles

In small portion of cases :
Dengue hemorrhage fever resulting bleeding, low level of platelets

Rx:

Acute Condition: Supportive (paracetamol)  and Oral or IV rehydration

• Do not prescribe Aspirin , Ibuprofen and Antibiotics ( Contraindicated) 

For Severe Cases: IV fluids and blood transfusion

Prevention: No vaccine but get rid if open source of water.

Difference between Primary aldosteronism and Secondary aldosteronism

Primary Aldosteronism

• Increase intravascular Volume
• Decrease RENIN Level
• Do not have pedal edema
• Hypertension

Secondary Aldosteronism

• Decrease intravascular Volume
• Increase RENIN level 
• Somtimes have Edematous state
• Hypotension

Swellings

Lipoma 

• Benign tumor from adipose tissue
• Commonest benign tumor
• Can be single or multiple(lipomatosis), usually encapsulated, slowly growing, soft swelling
• Usually painless. 
• Types 
• Painful lipomas are called neurolipomas . Dercum’s disease is tender deposition of fat especially on the trunk also known as adiposis dolorosa. It is basically neurolipomatosis.
• Fibrolipoma
• Nevolipoma 

Sites :

• Subcutaneous 
• Subfascial 
• Intramuscular
• Submucosal in GI tract
• Not present in brain

Clinical features

• Usually localized , nontender semifluctuant  mobile mass with edges slipping between palpating fingers 
• It is free from overlying skin
• Differential diagnoses
• Neurofibroma
• Sebaceous cyst
• Dermoid
• Lymph node enlargement

Complications

• Sarcomatous changes
• Saponification 
• Calcification 
• Submucosal lipoma can lead to intussusception

Treatment 

Excision 

Sebaceous cyst

• Retention cyst due to blockage of the duct of sebaceous gland
• Contains yellowish white cheesy material
• Common sites face , scalp and scrotum (not seen in palms and soles)
• Clinical features
• Painless swelling which is smooth, soft, nontender, freely mobile but adherent to skin over the summit, fluctuant, nontransilluminant and punctum over the summit (70%)
• It moulds on finger indentation 

Dermoid

Types :

1.Sequestration dermoid

• Cysts generally develops in line of embryonic fusion. So may be seen anywhere in midline, outer angle of dermoid, behind pinna or root of nose
• Clinical features- painless swelling in the line of embryonic fusion, soft, smooth, fluctuant and nontransillumintating with free skin

2. Implantational dermoid

• Due to minor pricks or trauma, epidermis gets buried into deeper subcutaneous tissue which causes reaction and cyst formation.
• Common in fingers , toes and feet
• Clinical features – swelling is painless , soft , tensely cystic nontransilluminating often adherent to skin

TREATMENT : Excision

Ganglion

• Cystic swelling containing clear gel formed by degeneration of synovial tissue.
• Occur in relation to tendon sheath or joint capsule
• Common sites: dorsum of wrist, flexor aspect of wrist
• Clinical features
• Well localized smooth, soft , cystic, nontender, transilluminant and mobile but mobility restricted when tendon is contracted against resistance

Treatment 
excision but high recurrence rate

Bursa

Bursa is a sac like cavity containing fluid within which prevents friction between tendon and bone

Minor injuries and pressure lead to bursitis which will present as swelling and  pain

Treatment excision if necessary

Neurofibroma 

• Tumor arising from connective tissue of the nerve.
• Can be single or multiple
• Types :
• Nodular neurofibroma – single, smooth, firm, often tender swelling which moves perpendicular to direction of nerve but not in the direction of nerve
• Plexiform neurofibroma – commonly occurs in the direction of Vth cranial nerve in skin of face . It attains enormous size with thickening of skin which hangs downwards.
• Generalised neurofibromatosis (von Recklinghausen’s disease) – it is inherited as autosomal dominant disease. Multiple neurofibromas associated with pigmented spots in skin (café au lait spots) . Associated with MEN type IIb   

Complications 

• Sarcomatous change – rapid enlargement, warm and vascular with dilated veins
• Cystic degeneration
• Hemorrhage into tissues
• Erosion of deeper structures
• Neurological deficits may occur

Treatment : excision for symptomatic , cosmetically problematic or malignant changes

Callosity and corn 

Callosity 

• raised thickened patch of hyperkeratosis common in areas which undergoes excessive wear and tear.
• Histologically there is increased thickening of epidermis particularly the stratum corneum and granular layer 

Corn 

• Circumscribed horny thickening cone-like in shape with its apex pointing inwards and base at surface.
• Occurs at the site of friction and often disappears spontaneously when causing factor is removed
• Histologically composed of keratin masses with intact basal layer
• Often caused by ill-fitting and tight shoes chiefly affecting feet and toes. 

Wart 

• Patches of overgrown skin with hyperkeratosis
• Usually occur in children and adolescents and young adults
• Growth occurs due to stimulation by HPV
• Main complaint is disfiguring 
• Frequently affects hands, face, knees, and sole (plantar warts) .
• Warts are usually firm and covered with rough surface and filifom excrescences.

NUTRITION

Caloric requirement in adults – 40kcal/kg/day

Carbohydrates 50% , fat  30-40% and protein 10-15%

Caloric value- carbohydrate and protein - 4kcal/g and fat – 9kcal/g

Indications of nutritional supplementation

• Preoperative nutritional depletion
• Burns
• Trauma
• Anorexia nervosa and intractable vomiting
• Pancreatitis, malabsorption, ulcerative colitis, pyloric stenosis
• High output intestinal fistulas
• Postoperative complications like sepsis, ileus and fistula
• Malignant disease

Methods of feeding

Enteral feeding

• GI tract is the best route to provide nutrition.
• Can be done 

i.Orally

ii.By nasogastric tube

iii.By enterostomy e.g. gastrostomy and jejunostomy in severe malnutrition, major surgeries, severe sepsis

Total parenteral nutrition (TPN)

Indications:

• Failure or contraindication for any enteral nutrition
• High output intestinal fistulas
• Major abdominal surgery of liver, pancreas, biliary tract, colon
• Septicemia
• Multiple trauma
• Short bowel syndrome
• TPN is given through central vein and not through peripheral vein
• Components used in TPN – carbohydrates, fat, aminoacids, vitamins and trace elements
• Contraindications :
• Cardiac failure
• Blood dyscrasias
• Altered fat metabolism

Complications of TPN 

1.Due to placement of CVP

• Air embolism
• Pneumothorax
• Bleeding
• Infection 
• Catheter displacement, sepsis, blockage, thrombosis

2. Biochemical

• Electrolyte imbalance
• Hyperglycemia
• Hyperosmolarity
• Dehydration
• Azotemia 
• Altered immunological function

3. Others

• Dermatitis
• Anemia 
• Cholestatic jaundice.

PRINCIPLES OF SKIN COVER - GRAFTS AND FLAPS

Characteristics

• Largest organ of the human body- surface area 1.5-2.0 sq.m,  2-3mm thick
• 15% of body weight
• Epidermis- Corneum, Lucidum, Granulosum, Spinosum, Basale,
• Dermis- papillary and reticular, made of collagen, 

Functions of skin

• Protective layer - Langhan’s cells of adaptive immune system
• Sensation
• Heat regulation
• Control evaporation
• Aesthetics 
• Makes vitamins D

When is skin required?

• Loss of large area of skin
• Large wound 
• Post burn raw area
• Release of contracture

Reconstructive Ladder

Graft and Flap

• Graft is free tissue without its vascular supply- skin, bone, tendon, nerve, vessels, muscle, fascia, mucosa
• Flap is tissue with its original blood supply
• Areas where we cannot put graft will need a flap-Flaps for bone devoid of periosteum, cartilage devoid of perichondrium, tendon devoid of paratenon

Grafting 

• Skin graft is essentially dead with no circulation. Under favourable conditions obtain new blood supply from recepient wound or defect. This is known as graft take
• Infection, pressure, hematoma or shear forces can result in graft failure
• Meshing – increase surface area and prevention of collections
• Immobilisation with Sutures / plaster slab
• Prevention of hematoma / seroma
• Dressing of recipient wound
• Donor site management

Process of graft take

1. Imbibition

2. Inosculation

3. Vascularization

Conditions affecting graft take

• Malnutrition- hypoproteinemia, vitamin deficiency
• Presence of hypertension, diabetes
• Compromised immune status
• Collagen vascular disease
• Constant pressure on the area

When to graft?

• Wound flat and red / can see the imprint of gauge piece
• No unhealthy granulation tissue or necrotic tissue
• Margins are healing and spreading
• Not much bleeding on touch
• dressing peels  with difficulty
• Bacterial count less than 105 
• No evidence of beta hemolytic streptococci

Types of skin graft:

Partial thickness- thin intermediate thick

Full thickness

Composite graft- More than one tissue type required to perform reconstruction

Split thickness skin grafting (Thiersch graft)

• Donor site heals spontaneously as part of dermis is left behind
• Contracture may occur
• Sensation function of hair sebaceous gland not present
• Donor area is dressed and dressing is removed after 10 days and after 5 days in recepient area

Skin graft harvesting

Instruments  -  Humby’s knife

Donor sites:

Thigh , legs, arm, forearm, body

Taking split skin graft with a Humby’s knife holder

Differences

Split thickness Skin graft:

• Epidermis and part of dermis
• Donor sites heal spontaneously 
• Extensive defects
• Graft take – good
• More contraction later
• Less stable
• Less colour and texture matching

Full thickness graft:

• Epidermis and whole dermis
• Donor site needs to be closed – direct or SSG
• Small defects
• Graft take – less readily- needs optimal condition
• Secondary contraction less
• More stable
• Good colour and texture matching

Full thickness skin grafting (Wolfe’s graft)

• Harvested with surgical blade
• Accurately fitted to the defect and sutured
• Donor sites – postauricular, upper eyelid, supraclavicular, flexural, abdomen
• Donor site closure
• Recipient site – dressing / immobilisation
• Whole thickness of skin is excised
• Defatting is done to improve graft take
• Blood supply must be restablished
• Where cosmesis is important (face) or flexibility is important (over joint)

Flaps

• Flap is tissue with its original blood supply

Classification:

1. Based on blood supply – 

• Random pattern (dermal and subdermal plexus)

Rotation flap / transposition flap / advancement flap

• Axial pattern (named vessel) e.g. groin flap (lat. Circumflex artery)

Peninsular flap / island / free flap

Free tissue transfer

• Most technically demanding
• Single stage wound closure
• Wide variety of flaps- tailored to coverage needs
• More acceptable aesthetic outcome

2. Classification based on tissue type
1. Cutaneous flap
2.Faciocutaneous flap
3.Muscle flap
4.Musculocutaneous flap
5.Osteocuaneous flap

3. Specialized flaps
1. Fascial flap
2. Vascularized bone flap
3. Functional muscle flap

Signs and Symptoms Associated with Down Syndrome

Down syndrome is the most common autosomal trisomy identified in liveborn infants. As many as 95% of Down syndrome cases arise due to chromosomal nondisjunction during maternal meiosis (47 XX, +21) an abnormality that positively correlates with increasing maternal age. Two of the more prominent and consistent lectures of Down syndrome are mental retardation and facial dysmorphism. Almost every organ and system, however, is affected

Signs and Symptoms Associated with Down Syndrome

Trisomy 21 (Down syndrome) is characterized by mental retardation, facial dysmorphism, single palmar crease, endocardial cushion defects, and duodenal atresia. Affected individuals have an increased risk of AML-M7 and ALL in childhood and early Alzheimer disease in adulthood. 

Difference between kawasaki and scarlet fever

Kawasaki disease include: (mucocutaneous lymph node syndrome)

Definition : Kawasaki disease is a vasculitis of medium-sized arteries that affects very young children (usually 12-24 months of age).

cause is unknown

Features:
1. Fever more than 5 days - even after aspirin
2. Bilateral conjunctivitis
3. Lymphadenopathy
4. Cutaneous involvement
1. Oropharyngeal: Erythema of the palatine mucosa, fissured erythematous lips, “strawberry” tongue
2. Peripheral extremities: Edema of hands and feet, erythema of palms and soles, desquamation of the fingertips (periungual)
3. Generalized rash: Polymorphous (usually urticarial) erythematous rash beginning on the extremities and moving to the trunk (centri petal spread)

Complication: Formation of coronary artery aneurysms is the most serious complication of Kawasaki disease.

Scarlet fever : 

Causes : Streptococcus pyogenes (group A streptococci) --Toxigenic

Features:

scarlet rash with Sand paper like texture ,circumoral pallor.

Tonsillar exudates, Spares the palms and soles

Complication: Septic complications

Aspirin helps to reduce fever , Amoxicillin and throat culture

Similarity : ''Strawberry tongue''

The Gallbladder and bile ducts

Gallbladder

• The gallbladder is a pear-shaped reservoir in continuity with the common hepatic and common bile ducts through the cystic duct.
•  It is usually 7.5 to 12cm in length, is 3 to 5 cm in diameter, and has a capacity of 35 to 50 mL.
•  The gallbladder lies on the inferior surface of the liver partially enveloped in a layer of peritoneum.
•  The gallbladder is anatomically divided into the fundus, body, infundibulum, and neck, which empties into the cystic duct.
•  Both the gallbladder neck and the cystic duct contain spirally oriented mucosal folds known as the valves of Heister. 
• The valves prevent the passage of gallstones and excessive distention or collapse of the cystic duct, despite variations in ductal pressure. 

The Hepatic Duct (ductus hepaticus)

• Two main trunks of nearly equal size. Arising from the liver at the porta. one from the right, the other from the left lobe.
• The common hepatic duct is less than 2.5cm long  and is formed by the union of the right  and left hepatic ducts.
• It passes downward and to the right for about 4 cm.
• Joined at an acute angle by the cystic duct to form the common bile duct. Lies between  the layers of the lesser omentum.
• Is accompanied by the hepatic artery and portal vein. 

Cystic duct

The cystic duct varies in length from 1 to 5 cm and in diameter from 1 to 3 mm; it usually joins the common hepatic duct at an acute angle.

The Common Bile Duct 

The common bile duct is formed by the junction of the cystic and hepatic ducts.

• Length: It is about 7.5 cm. long.
• Diameter: That of a  goose-quill.

• Course and extent : It descends along the right free margin  of the lesser omentum along with   portal vein ( which is behind it ) , and to the right of the hepatic artery. 
• Then behind the superior portion of the duodenum,
• After crossing the duodenum, it runs on the posterior surface of the head of the pancreas, and in front of IVC. 
• Occasionally completely imbedded in the pancreatic substance. 
• At its termination it lies for a short distance along the right side of the terminal part of the pancreatic duct and passes with it obliquely between the mucous and muscular coats. 
• The two ducts unite and open by a common orifice upon the summit of the duodenal papilla, situated at the medial side of the descending portion of the duodenum, a little below its middle and about 7 to 10 cm. from the pylorus. The short tube formed by the union of the two ducts is dilated into an ampulla, the ampulla of Vater. 

Blood supply

• Gall bladder is supplied by Cystic artery, a branch of right hepatic artery.
• The blood supply to the common hepatic duct, cystic duct and common bile duct comes from the gastroduodenal, retroduodenal, postero-superior pacreatico duodenal arteries. 

Lymphatics

• The lymphatics of gallbladder (subserosal and submucosal) drain into the cystic L/N of Lund.
• Small veins and lymphatics course between the gallbladder fossa and the gallbladder wall, connecting the lymphatic and venous drainage of the liver and gallbladder. These connections are the cause of the direct inflammatory and carcinomatous spread from the gallbladder into the liver.

Calot’s triangle

Formed by:

• Common hepatic duct to the left
• Cystic duct below and 
• inferior surface of the liver above.

Content:

• the cystic artery, 
• the right hepatic artery, and
• the cystic duct lymph node.

Functions of gall bladder

• Stores bile
• Concentrates bile
• Secretion of mucus

Embryology

• The hepatic diverticulum arises from the ventral wall of the foregut and elongates into a stalk to form the choledochous.
• A lateral bud is given off, which becomes the gall bladder and the cystic duct.

Congenital abnormalities

• Absence of the gall bladder
• The Phrygian cap
• Floating gall bladder
• Double gall bladder
• Absence of the cystic duct
• Low insertion of the cystic duct
• An accessory cholecystohepatic duct

Biliary atresia

It may be due to viral infection or defective embryogenesis resulting in the inflammatory destruction of extra- and intrahepatic biliary tree.
Incidence 1 in 12000 live births
Male and female equally affected.
It may be associated with: cardiac lesions, polysplenia, situs inversus, absent vena cava and a preduodenal portal vein.

Classification

Type I: atresia restricted to the common bile duct
Type II: atresia of the common hepatic duct
Type III: atresia of the right and left hepatic ducts

Clinical features

• Progressive jaundice in a new born.
• Steatorrhea
• Osteomalacia
• Biliary rickets
• Severe pruritus
• Clubbing and skin xanthomas

D/D

• Alpha 1-AT deficiency
• Cholestasis associated with i.v feeding
• Choledochal cyst
• Inspissated bile syndrome
• Neonatal hepatitis

Treatment
In correctable cases:
Roux-en-Y hepaticojejunostomy
In noncorrectable cases:
Hepaticoportojejunostomy (Kasai’s operation)
Radical excision of all bile duct tissue up to the liver capsule is performed.
A roux-en-Y loop of jejunum is anastomosed to the exposed area of liver capsule above the bifurcation of the portal vein creating a portoenterostomy

Liver transplantation: in case of unsuccessful

Caroli’s disease

It is a congenital, multiple, irregular dilatations of the intrahepatic ducts with stenotic segments in between.
Extrahepatic biliary system is normal.

Types :

Simple type
Presents later with episodes of aqbdominal pain and biliary sepsis

Associated with:
Congenital hepatic fibrosis
Polycystic liver
Cholangiocarcinoma
Periportal fibrotic type
Presents in childhood

Periportal fibrotic type is associated with:
Biliary stasis
Stone formation and
Cholangitis

T/T

• Antibiotics for chalangitis and removal of calculi.
• If limited to one lobe of liver- lobectomy

Choledochal cyst

Choledochal cysts are congenital dilations of the intra- and/or extrahepatic biliary system.

Classification (Todani)

Type Ia and b: diffuse cystic
Type II: diverticulum of the common bile duct
Type III: diverticulum within the pancreas
Type IV: extension into the liver
Type V: cystic dilatation only of the intrahepatic ducts

Clinical features

• Can occur in any age.
• Patients may present with jaundice, fever, abdominal pain.
• O/E right upper quadrant mass which is smooth, soft, not moving with respiration, not mobile and resonant.

Ix

Ultrasonography abdomen:
Confirms the presence of  abnormal cyst

MRI/MRCP:  
reveals anatomy. Esp. relationship between the lower end of the bile duct and the pancreatic duct.

CT: 
show the extent of intra- and extrahepatic dilatation.

Treatment
Radical excision of the cyst is the t/t of choice with reconstruction of the biliary tree using a RouX-en-Y loop of jejunum.

CNS sequelae of hypertension

Charcot-Bouchard aneurysms are microaneurysms that are less than 1 mm in diameter. They occur in the small penetrating arterioles that perfuse the basal ganglia, pons and subcortical white matter. These aneurysms occur due to long-standing hypertension and are prone to rupture. Hemorrhagic stroke would be evident on the intial CT scan as a focus of intraparenchymal hyperdensity.

Lacunar infarcts are small ischemic infarcts ( less than 15 mm in diameter), usually involving the basal ganglia, pons, internal capsule, or deep white matter of the brain. Lacunar infarcts occur most often due to hypertensive arteriolosclerosis of small, penetrating arterioles.

Neonatal complications of diabetes during pregnancy

• Premature delivery
• Fetal macrosomia
• Neural tube defects (e.g Caudal regression syndrome)
• Hypoglycemia
• Hypocalcemia
• Polycythemia
• Respiratory distress
• Transient hypertrophic cardiomyopathy.

Gram positive Cocci Classification

Sexual appearance of fetus at (second to third month) (third to fourth) and (at time of birth) of pregnancy

Sexual appearance of fetus at (second to third month) (third to fourth) and (at time of birth)of pregnancy.

Homocystinuria

Homocystinuria is caused by cystathionine synthetase deficiency. Affected individuals manifest with skeletal abnormalities resembling those of Marfan syndrome. In addition, they are also at high risk of developing thromboembolism. About 50% of affected patients respond to high doses of vitamin B6 (pyridoxine).

Homocystinuria is the most common inborn error of methionine metabolism and is caused by cystathionine synthetase deficiency. Thromboembolic episodes involving both large and small vessels, especially those of the brain, are classically associated with this condition and may occur at any age. Other clinical manifestations resemble those of Marfan syndrome. These include ectopia lentis, elongated limbs, arachnodactyly, and scoliosis.

Glycogen storage diseases

Polycistronic mRNA (Bacterial lac operon)

Bacterial mRNA can be polycistronic, meaning that one mRNA codes for several proteins. An example of polycistronic mRNA is the bacterial lac operon, which codes for the proteins necessary for lactose metabolism by E. coil; the transcription and translation of these bacterial proteins is regulated by a single promoter, operator, and set of regulatory elements. 

Multiple origins of replication (DNA replication)

The process of DNA replication is similar in eukaryotes and prokaryotes. The key steps involved in DNA replication are:
1. Unwinding of double stranded DNA (dsDNA) by helicase to produce single stranded DNA (ssDNA)
2. Formation of a replication fork
3. Formation of an RNA primer by the action of the enzyme primase
4. Synthesis and concurrent proofreading of daughter DNA strands by DNA polymerases
5. Ligation of Okazaki fragments on lagging strands by ligase and removal and replacement of RNA primers with DNA by DNA polymerase I
6. Reconstitution of chromatin and ligation of daughter strands.

In E. coil, a prokaryote, the three major types of DNA polymerase are DNA polymerase I, II and III. In eukaryotes there are five major DNA polymerases: alpha, beta, gamma, delta and epsilon. Though the eukaryotic genome is much larger and more complex than the prokaryotic genome, interestingly the size of the eukaryotic genome is not the source of its complexity. Its complexity results from the presence of a large number of non-coding DNA regions between coding regions. Within genes there are introns (Non-coding regions - Think “IN” between) separating exons (Coding regions - Think “EX” pressed). Prokaryotes rarely have introns within their genes.
In contrast to prokaryotes which typically have a single origin of replication eukaryotes have multiple origins of replication? With multiple origins of replication, the genome can be copied much more quickly because multiple regions are being replicated at once. 

Bilirubin metabolism