1. Ravinder Kumar Batra Professor Department of Anaesthesiology, AIIMS
Obstructive Jaundice
Ravinder Kumar Batra
Professor
Department of Anaesthesiology, AIIMS

2. Chief Complaints 4O yr male presented with :
Yellow coloration of Eye -8 months
Yellow coloration of urine – 8 months

3. History of present illness
Gradually progressive yellowish coloration eye
Recurrent episode of itching
White stools 4 months back, persisted for 2 months
Abdominal pain- Right upper quadrant- 6 months
Generalized weakness & fatigability- 6 months
Weight loss kg in 7 months
Reduced appetite
No fever

4. H/o past illness
Typhoid fever – 9 months back
No h/o DM, HT, TB, Chest pain
No previous surgery
Personal History
Normal Bowel & bladder habits
Smoker – 25 yrs
Non-alcoholic
Effort tolerance good

5. Important points in History
Duration of Jaundice
Progress & previous attacks of jaundice
Prodrome
Fever
Abdominal pain: Biliary/pancreatic/Dull
Pruritis, Colour of urine and stool
Drug ingestion
Manifestations of fat soluble Vit deficiency
Weight loss
Vitamin deficiency: A; night blindness. D: bone pain & muscle weakness: E: leg cramps, K: Easy bruising
Jaundice: sudden or gradual, first noticed at place
Progressively worsening jaundice- Malignancy, primary biliary cirrihosis, familial cholestasis, primary sclersing cholangitis, advanced end stage liver disease,
Intermittent jaundice: choledocholithiasis, ampullary carcinoma ( sloughing of tu mass), biliary ascariasis, relapsing viral hepatitis
Sudden onset, progressive steadily deepening obstructive jaundice, weight loss – malignancy

6. History suggestive of Normal colored urine/cola color in hemolysis
Recurrent episodes
Recurrent anaemia
No prodrome
Pain
Chills, fever, systemic illness
Biliary surgery
Unconjugated hyperbilirubinemia/hemolysis
Clay stools – complete biliary obstruction
weight loss and its significance – 5% is considered significant, loss of appetite and ass with malignancy
Abdominal pain: suggests extrahepatic cause of cholestasis:
Biliary colic: severe intermittent colicky pain It is a visceral pain, which is steady rather than intermittent, usually in the epigastrium and right upper quadrant, increases over a period of 15 min to 1hour or more, and then slowly resolving within 6 hours.
Pancreatic pain: Dull, continuous pain radiating to back, aggravated by food, and relieved by sitting up or leaning forward.
Dull, continuous, dragging type of pain in right hypochondrium- stretching of Glisson capsule due to hepatomegaly.
Prodromal symptoms at or before onset: Suggestive of viral hepatitis/drug induced hepatitis
Gradual or sudden, how much weight loss and its significance
Generalized pruritis, Clay coloured stool and tea coloured urine
Bile duct stones/cholangitis/obstructive jaundice

7. History suggestive of Cholestasis Contact with other jaundiced patient
History of injections or blood transfusions
Exposure to drugs
Prodrome of anorexia, nausea, vomiting
Pruritis
Clay coloured stools
VH/Drug induced Hepatitis
Clay stools – complete biliary obstruction
weight loss and its significance – 5% is considered significant, loss of appetite and ass with malignancy
Abdominal pain: suggests extrahepatic cause of cholestasis:
Biliary colic: severe intermittent colicky pain It is a visceral pain, which is steady rather than intermittent, usually in the epigastrium and right upper quadrant, increases over a period of 15 min to 1hour or more, and then slowly resolving within 6 hours.
Pancreatic pain: Dull, continuous pain radiating to back, aggravated by food, and relieved by sitting up or leaning forward.
Dull, continuous, dragging type of pain in right hypochondrium- stretching of Glisson capsule due to hepatomegaly.
Prodromal symptoms at or before onset: Suggestive of viral hepatitis/drug induced hepatitis
Yellowish: sudden or gradual, first noticed at place
Gradual or sudden, how much weight loss and its significance
Generalized pruritis, Clay coloured stool and tea coloured urine
Cholestasis

8. Examinations General Physical Examination:
Pulse 88/min,BP 110/ Pallor +, Jaundice +
No Lymphadenopathy
Per abdomen
Soft non-tender
Gall bladder palpable
Liver: 3cm below costal margin
No free fluid

9. Airway Examination MMP grade II Mouth opening: Adequate
Teeth intact, no loose tooth
Fever: Fever at onset-viral hepatitis; fever with rigors-chlangitis; lowgrade fever- neoplasm
drugs and injections:
Cholestasis- OC, anabloic steroid, , chlorpromazine, carbamazepine, antibiotics- erythromycin, rifampicin
Hepatitis- INH, halothane, phenytoin, methyldopa
Fatty liver- tetracycline, valproate
Toxic necrosis- acetoaminophen,CCl4
H/o GI bleeding indicates ampullary malignancy or development of portal HT
Fever: Fever at onset-viral hepatitis; fever with rigors-cholangitis; low grade fever- neoplasm
What drugs and injections:
Bland cholestasis- Prodrome followed by pruritis, SAP>3xULN times, mildly elevated AST/ALT. ALT/SAP ratio<2, serum bilirubin<12mg%.
Estrogen, Tamoxifen, anabloic steroid, Azathioprine
Cholestasis with hepatitis- Pain in right hypochondrium with jaundice;SAP>3ULN, ALT>2-3xULN, ALT/SAP ratio between 2-5 times): Phenothiazines, Tricyclic antidepressants, Macrolide antibiotics, Amoxixillin-clauvulanate, Azathioprine
Cholestasis with bile duct injury: Dextrpropoxyphene, Flucloxacillin
Vanishing bile duct:( Cholestasis like primary biliary cirrhosis, but AMA negative)- Chlorpromazine, Flucloxacillin, Amoxixillin-clauvulanate, Carbamazepine, Phenytoin, phenobarbital, Azathioprine
Large duct stricture( like primary sclerosing cholangitis)- Floxuridine, Intralesional scolicidal agent, ( formalin, silver nitrate, hypertonic saline, absolute alcohol, iodine solution.
Manifestations of FSVD: VitaminA- night blindness, Vitamin D- Bone pain & muscle weakness, Vitamin E- leg cramps, Vitamin K- easy bruising.

14. General Examination Body mass index Vital signs: Pulse
Pallor: GI bleeding, Hemolysis
Icterus
Pedal oedema: hypoproteinemia/cirrihosis
Shiny nail & scratch marks (pruritis)
Xanthoma
Ecchymosis, Bitot spots (Vitamin deficiency)

15. Abdomial Examination Abdominal distension, distended veins, scar
Hepatomegaly
Splenomegaly
Gall bladder or any mass,
Free fluid

16. Define Jaundice and where all you will look for this?
Bilirubin has high affinity to elastin, and scleral tissue is rich in elastin , therefore scleral icterus is a more sensitive sign of hyperbilirubinemia than generalised jaundice
Sites: Sclera, undersurface of the tongue, palms, nails, skin

17. Excess plasma bilirubin Normal range < 1 mg/dl
Yellowish pigmentation of the sclera, skin, mucous membrane & other tissues: Jaune
Excess plasma bilirubin
Normal range < 1 mg/dl
(I: mg/dl;D:0.1—0.4mg/ dl, <5% in Conjugated form)
Clinically obvious 2-3 mg/dl
Sites – Sclera, undersurface of the tongue, palms, nails, skin, hard-palate
High Affinity for Collagenous tissue
Bilirubin has high affinity to elastin, therefore scleral icterus is a more sensitive sign of hyperbilirubinemia than generalised jaundice
Sites: Sclera, undersurface of the tongue, palms, nails, skin
D/D – carotemia, treatment with quinacrine, no scleral icterus 

18. Describe Bilirubin Formation & Excretion?

19. Bilirubin Metabolism Bilirubin production: 250-350mg/day
Ret En System Plasma Liver Bile
Heme oxygenase Biliverdin reductase
Haem BVD UCB UCB UCB
Albumin
70% 30% BMG BMG
BMG & BDG
Hb other BDG BDG
haemoproteins
Glomerulus Urine
Bilirubin production: mg/day

20. Portal vein
the conjugated bilirubin is hydrolyzed and converted to urobilinogen by the intestinal pathogens.
The urobilinogen is then oxidized to orange-color stercobilin and excreted in the stool. The yellowish color of stool is the color of the sterocobilin. Therefore, the clay color stool means that there is no bilirubin coming from biliary ducts owing to the obstruction of the bile ducts.
About 15 ~ 20 % of the urobilinogen is reabsorbed from the intestine into portal veins and finally 90 % of it is returned to the liver and is re-excreted in the bile, this is called entero-hepatic circulation of bilirubin. The remainding 10 % gets into the systemic circulation and finally exreted in the urine through kidney as urobilin.
In obs. J the conj bil enters the gen cir. through hepatic vein and is excreted in urine.

21. How will you Differentiate the three types of Jaundice Biochemically?

22. Features
Prehepatic (hemolytic)
Intrahepatic Heptocellular
Post-hepatic (Obstructive)
UCB ↑
Normal CB
AST or ALT ↑↑
SAP
Urine Bilirubin
Absent
Present
Increased
Urobilinogen

23. Features
Prehepatic (hemolytic)
Intrahepatic Heptocellular
Post-hepatic (Obstructive)
Plasma Albumin
Normal
Decreased
Normal or decreased PT
Increased
Increased but correccted by Vitamin K

24. How will you Evaluate a Case of Jaundice?

25. HISTORY clinical evaluation
AST, ALT, ALP
Hemolysis Vs Cong
Hyperbilirubinemia
Normal
Abnormal
USG if biliary obstruction is suspected
Non-dilated ducts
Dilated ducts
Biliary Obstruction
Hepatocellular jaundice
Evaluation for:
Acute vs Chronic
Etiology
Evaluation for:
Cause
Extent
BILIRUBIN
GGT, Viral Markers, Autoimmune Markers Liver Biopsy
ERCP, MRCP, PTC, CT

26. Investigations Bilirubin, Serum enzymes (SGOT, SGPT)
SAP, GGT, 5-nucleotidase
Proteins: Albumin, Globulins, INR or PT, markers
Ultrasound, CT scan
ERCP
Percutaneous Transhepatic Cholangiography
Magnetic resonance cholangiopancreaticography
Liver Biopsy

27. What are the Pathophysiological consequences of Obstructive / Cholestatic Jaundice?

28. Consequences of Cholestasis
Retention of bile salt in liver
Decreased hepatocyte function
Dysfunction of Cyto -450
Albumin & clotting factors synthesis decreased
Decreased Kuffer cell activity
Bile constituents in serum
Jaundice, Pruritis
CVS depression
Nephrotoxicity
Hypercholesterolemia, atheroma, Xanthoma
Pruritis: Exact pathology is not known:
Central mechanism: Increase central opioidoergic tone in patients with cholestasis
Peripheral Mechanism: accumulation of numerous substances (bile acids, histamine, serotonin & endogenous opioids) in the systemic circulation subsequent to failure of elimination

29. Consequences of Cholestasis
Absence of bile in Intestine
Escape of endotoxins into portal blood
Malabsorption of fats, Vit A, D, E & K
Clay colored stools
Pruritis: Exact pathology is not known:
Central mechanism: ↑ central opioidoergic tone
Peripheral: accumulation of bile acids, histamine, serotonin & endogenous opioids
Pruritis: Exact pathology is not known:
Central mechanism: Increase central opioidoergic tone in patients with cholestasis
Peripheral Mechanism: accumulation of numerous substances (bile acids, histamine, serotonin & endogenous opioids) in the systemic circulation subsequent to failure of elimination

30. Anaesthetic Problems associated with Obstructive Jaundice

31. Anaesthetic Problems: CVS
Impaired myocardial contractility
Bradycardia
Vasodilatation  ↓ ability to mobilise blood from splanchnic vasculature during haemorrhage
↓ sensitivity to vasopressors
 Hypotension & circulatory collapse
Small blood losses poorly tolerated
Replace volume losses immediately in perioperative period
bradicardia

32. Anaesthetic Problems: Renal system
Etiology Multifactorial
Arterial hypotension-myocardial depression
Reduction in intravascular volume
Nephrotoxicity - bile salt, endotoxins & Inflammatory mediators
Incidence 5 -10%, mortality: 32 – 100%
Level of hyperbilirubinemia correlates with postoperative decrease in creatinine clearance

33. Anaesthetic Problems: Sepsis
Associated cholangitis and bactibilia
Escape of endotoxins from intestine  portal blood
↓ kuffer cell activity
Prevention
Perioperative antibiotics
Preoperative oral bile salts

34. Anaesthetic Problems: Coagulopathy
• Vit. K malabsorption
(Activation II,VII,IX,X )  ↑ PT
Pre-op. Vit. K 10 mg OD × 3 days
• long lasting biliary obstruction  Sec. biliary cirrhosis  ↓ syn. of coag factors
(poor prognosis)  transfusion of FFP
Vit K acts as cofactor in synthesis of coagation factors by gamma- carboxylation of glutamate residues

35. Anaesthetic Problems Multiple Vitamin Deficiency - A, D, E, K
( A - night blindness ,D – osteoporosis and ms weakness, E- leg cramps ,K- easy bruising )
Haemorrhagic gastritis and stress ulcer
Impaired wound healing
Altered drug handling due to cholestasis
Long standing extrahepatic biliary obstruction > 1yr → biliary cirrhosis → problems of liver dysfunction

36. Investigations for Assessing Liver Functions?

37. Assessment for liver cell injury
S. Bilirubin
Transaminase SGOT/SGPT – 35 IU/L
SGOT -extrahepatic- heart/sk ms/kidney/brain:less specific
SGPT - primarily found in liver, more specific
Alcoholic hepatitis SGOT/SGPT > 2 (deficiency of pyridoxine-5-PO4 )
Alkaline phosphatase – 35 – 100 IU/L
Extrahepatic- bone, intestine, liver, placenta
5- Nucleotidase - confirms hepatic origin of ALP
Gamma Glutamyl Transpeptidase – most sensitive indicator of biliary tract disease
UNCONJ BIL> 80% - UNCONJ HYPERBILIRUBINEMIA
CONJ BIL > 50% - CONJ HYPERBILIRUBINEMIA
In general SGOT & SGPT levels parallel each other
AST/ SGOT, ALP/SGPT , GAMMA GLUTAMYL TRANSPEPTIDASE

38. Aminotransferases Alk PO4 Diag. Likelihood
Viral hep Obstr.
> X 6 < X % 10%
< X 6 > x % 80%
Parenchymal diseases ultimately produce an obstructive component & Long standing Obstructive diseases cause cellular dysfunction

39. Assessment of Synthetic Ability of Liver
• Prothrombin time – factors II, VII, IX & X
short t ½ hr
Good Indicator of liver fn. in both Acute & Chronic
Liver disease.
D/D - Obst. jaundice parentral vit. K → PT normalises
in 24 – 48 hrs
• Serum albumin – t ½ life days
Liver – substantial reserve for alb. syn.
Not a good indicator for acute or mild liver damage
Indicator of severity of chronic liver disease
< 2·5 gm% - severe damage
Albumin - Albumin daily prod. 10—15g/d ( gm%)
Function – Plasma oncotic press. ,transport vehicle, Drug binding

40. What are the other Preoperative Investigations required ?

41. Preoperative Investigations
Hb - ↓ in concealed blood loss, haemolysis,
TLC, DLC - ↑ infection
Platelet Count , clotting studies - PT, PTTK
Urea, S. Creatinine, Electrolyte
HBV, HCV
Chest X-ray, ECG, blood gases
Severe acute & chr. Liver disease are chr. By failure to syn urea & fall in its plasma conc. & rise in conc. Of ammonia.

42. Investigations Hb-9.7, TLC-16200, PC-4.56 Lac
LFT-S.Bil T-14.0/D11.3/2.7
SGOT/SGPT-183/81, SAP-1493
Urea/Creatinine: 15/1
PT : normal
CxR: Normal
CA-19-9: 10.6U/ml ( u/ml –male)
Side View Endoscopy: Ampulla bulky friable, ulcerated
Ampullary Biopsy: Few displasia & atypical cells

43. Investigations
USG-Abd: solid mass in distal CBD, dilated CBD, Intrahepatic Biliary distension with distended GB with hepatomegaly
Dual Phase CT: Mass at lower end of CBD with dilated upper stream Biliary system
Endoscopy US: Mass in uncinate process likely malignant

44. CT imaging

45. CT imaging

46. CT imaging

47. CT imaging

48. CT imaging

49. CT imaging

50. Case : Diagnosis
Periampullary Carcinoma

51. What are Troisier’s sign and Courvoisier’s law?

52. Troisier’s sign Enlargement of Left Supraclavicular Lymph Node due to
Secondary involvement seen in malignancies of
G.I.T., Breast and Testis.

53. Courvoisier’s law
If the CBD is obst. due to calculus , the GB is usually not distended owing to previous inflammatory fibrosis.
In obstr. of the CBD due to growth, the GB becomes distended in order to reduce the press. in the biliary system.

54. What are the Surgical Procedures done for Obstructive Jaundice?

55. Ca GB: Radical Cholecystectomy with wedge ressection and CBD excision
Choledocholithiasis: ERCP removal or CBD exploration/ bilio-enteric anastmosis
Cholangio Ca: Liver resection and or local excision of the lesion or Whipple
Biliary Stricture: Hepatico-jejunostomy/ liver resection

56. Periampullary Ca:
Whipple’s Procedure
Chronic Pancreatits with head Mass: Whipple/ bilio-enteric anastmosis

57. Whipple’s Procedure Pancreaticojejunostomy- end to end
Hepatico-jejunostomy – end to side
Gastrojejunostomy – end to side
Feeding Jejunostomy

58. What are the Risk factors for Operative Mortality in these patients?

59. Preoperative Risk factors
Dixon etal – GUT 1983
Hematocrit < 30 %, S. bilirubin > 12mg%
Malignant cause of biliary obstruction
Mortality 60% if above present, 5 % otherwise
Blamey et al 1983 : Brit J of Surg 8 factors
Age >60 , Malignant D, S Bil> 6mg/dl, Hct <30%, TLC>10000, S. alb <3, S creatinine>1.5, SALP >600
Multivariate analysis and retrospective study of 373 pts. By Dixon etal – 1983 identified Hematocrit < 30 %
S. bilirubin > 11mg%, Malignant cause of biliary obstruction as predictors of periop mortalily. If all these were present – 60%, none – 5%.OTHER Preop predictors of poor surgical outcome include -
If all first 3 are present – 60%, none – 5%

60. Preoperative Risk factors
Bose et al Ind J Surg 1990
Age >60, Associated DM, Previous Biliary tract surgery & prolonged surgery
Friedman –Hepatology June1999
Azotemia, Hypoalbuminemia & Cholangitis
Multivariate analysis and retrospective study of 373 pts. By Dixon etal – 1983 identified Hematocrit < 30 %
S. bilirubin > 11mg%,Malignant cause of biliary obstruction as predictors of periop mortalily. If all these were present – 60%, none – 5%.OTHER Preop predictors of poor surgical outcome include -
If all first 3 are present – 60%, none – 5%

61. What are the anaestheic goals in surgery for an Obstructive Jaundice patient ?

62. Anaesthetics Goals Maintain
Hepatic oxygen supply – demand relationship
Renal function

63. MANTAINING HEPATIC BLOOD FLOW
AVOID :
Sympathetic stimulation
Hypotension (decreased venous return / cardiac output) caused by :
Haemorrhage
Cardiac depressant drugs
Regional anaesthesia e.g.; thoracic epidural analgesia
Hypocapnia
Pressure effects caused by
Surgical retraction
Tumors
Ascites / Laparoscopy
Hepatic venous congestion caused by
Head down position, IPPV, Rt. side heart failure

64. Maintaining Renal function
Preoperatively
Avoid NSAIDs & nephrotoxic antibiotics e.g.; (aminoglycosides)
Oral bile salts to normalize gut flora
Prophylactic antibiotics to prevent sepsis
Drainage stent -↓ Hyperbilirubinaemia
PTC, ERCP or papillotomy
Intraoperatively
Avoid hypotension & hypoxaemia
Avoid dehydration
Renal dose dopamine? mannitol/furosemide

65. Preoperative preparation
Anxiolytic – oral short acting BDZ
Oral H2 antagonist
Vit. K (Obst. J) – 10 mg OD X 3 day, FFP
Perioperative broad spectrum antibiotics
Oral bile salts

66. Preoperative preparation for Anaesthesia
Rehydration and adequate diuresis 1ml/kg/hr
If Bilirubin > 8 mg% –
I/V fluid – 1-2 ml/kg/hr.
Furosemide/ Mannitol
Catheterization & CVP monitoring

67. Choice of Anaesthesia?

68. Choosing appropriate anaesthetic agent
No drug is contraindicated in Cholestatic liver disease per se
Other considerations
Coexisting hepatocellular disorder
Renal dysfunction
Drugs ↑ cholestasis e.g.; chlorpromazine
Anaesthetic agent of choice
Not dependent on hepatic metabolism
Maintains hepatic O2 supply – demand relationship

69. General anesthesia Induction agent - Thiopentone/Propofol
slow titrated dose → avoid hypotension
→ avoid symp. Stimulation during intubation
Muscle relaxant
Suxamethonium - RSI
Atracurium (DOC) - Hoffman’s elimination
Vecuronium

70. Anaesthetic technique
Opioids
fentanyl (DOC)- maintains hepatic oxygen supply – demand
spasm of sphincter of Oddi – incidence < 3%
Bil. colic , false + cholangiogram
T/T naloxone, glucagon, atropine, nitroglycerine
Volatile Anesthetics
Isoflurane - maintains HBF & oxygen supply
IPPV –- Maintain eucapnia
Avoid high airway pressures

71. Metabolism & Elimination of Ms Relaxants
Drug
Duration
Metab.
Eli. Kid. %
Eli. Liv. %
Sch
Ultrashort
Butyrylcholinestras 99%
<2
None
Atra
Intermediate
Hoff & ester % Urine & Bile
10-40
Cis
Hoff 77%
16%
Vec
Liver 30-40% Urine & Bile
40-50
50-60
Roc
Long
10-20 85 15
dTc
80%?
20%

72. Regional anaesthesia as supplement to G.A.
Epidural anaesthesia : Concerns
Coagulopathy
Hypotension

73. Intraoperative Monitoring

74. Intra Operative Monitoring
Longer & extensive surgeries
Intra arterial and CVP
Biochemical: B.Sugar, ABG, Electrolytes
Hematology: Hb, PT, PTTK, TEG
Routine
• ECG, NIBP
SaO2, EtCO2
Urine output
Temperature
NMJ monitoring

75. Post-operative Management?

76. Postoperative management
Conscious, adequate NM recovery, vitals stable→ extubate → oxygen - enriched air
Else - Continue IPPV
- Correct Fluid & Electrolyte imbalance
- Correct hypothermia
- Achieve CVS stability
Adequate analgesia & chest physiotherapy
Antibiotics + H2 receptor antagonist
Maintain urine output
Replace blood and blood products

77. What are the Causes of Cholestasis: Intrahepatic & Extrahepatic

78. Extrahepatic: Benign causes
Choledocholithiasis
Primary sclerosing cholangitis
AIDS Cholangiopathy
Post-surgical stricture
Pancreatitis

79. Extrahepatic: Malignant Causes
Carcinoma gall bladder
Periampullary Carcinoma
Cholangiocarcinoma
Carcinoma of the head of pancreas
Obstruction of the drug due to metastatic LN

80. Intrahepatic cholestasis
Cholestasis phase of AVH
Alcoholic H
Drug induced liver D
Primary biliary cirrhosis
Primary sclerosing cholangitis
TPN

81. Intrahepatic cholestasis
Graft-versus-host D
Cholestasis of pregnancy
Sepsis
Benign postoperative Cholestasis
Fibrosing cholestatic hepatitis.

82. Name the Drugs that lead to Cholestasis Jaundice?

83. Drugs that lead to Cholestasis Jaundice?
Estrogen
Tamoxifen
Anabolic steroid
Azathioprine
Chlorpromazine
Carbamazepine
Antibiotics- Erythromycin, Rifampicin

84. Name the Conditions where Family H/o of jaundice is present?

85. Family H/o Jaundice
Progressive Familial Intrahepatic Cholestasis syndrome
( Dublin Johnson’s and Rotor’s syndrome)
α- antitrypsin deficiency
Wilson’s Disease ( Hepatolenticular degenertion- copper accumulation)

86. Describe the structural/ architectural and the functional units of liver.

87. Hepatic lobule: Str. Unit
The lobule is the structural unit of the liver . It is easy to observe under microscope and roughly hexagonal in shape, with portal triads at the vertices and a central vein in the middle.
Portal lobule comprises of adjoining parts of 3 hepatic lobule with center around portal triad
Hepatic lobule: Str. Unit

88. Zone 1-Richer in O2 and nutrients
Zone 3-poorer in O2 and nutrients
The hepatic acinus represents functional unit because it is oriented around the afferent vascular system .the hepatocytes in acinus are divided into zones that correspond to distance from the arterial blood supply .those hepatocytes closest to the arterioles in zone 1 are the best oxygenated, while those farthest from the arterioles in zone 3 have the poorest supply of oxygen.
Hepatic Acinus : Func. Unit - divided into zones that correspond to distance from the blood supply

89. Zone I – Periportal –
↑ mitochondria
Oxidative and phase 2 metabolism, glycogen synthetase
Zone 3 - Centrilobular
↑ SER, cyt-P-450, NADH
Anaerobic & phase 1 metabolism
Most sensitive to injury from circulatory disturbances and toxic byproducts

91. Isolated elevation of S.Bilirubin
Unconjugated hyperbilirubinemia
Increased Bil Production (Hemolysis)
Ineffective erythropoiesis, resorption of hematoma
Decreased hepatocellular uptake (Rifampicin)
Decreased conjugation (Gilbert & Crigler-Najjar)
Conjugated hyperbilirubinemia
Dubin Johnson Syndrome and Rotar syndrom

92. Hepatocellular Jaundice
Acute or subacute hepatocellular injury
VH, alcohol, drugs, ischemic hepatitis, Wilson’s disease, acute fatty liver of pregnancy
Chronic hepatocellular disease
VH, Alc liver D, autoimmune H, Wilson’s disease
Non-alcoholic steatohepatitis, α-antitrypsin deficiency

93. Hepatocellular Jaundice
Hepatic disorders with prominent cholestasis
Diffuse infiltrative disorders: granulomatous D –myobacterial infestions, sarcoidosis, lymphoma, drugs, amyloidosis, malignancy
Inflammation of the intrahepatic bile ductules &/or portal ducts (primary biliary cirrhosis), graft-vs host D, chlorpromazine

94. Hepatocellular Jaundice: Miscellaneous
Benign recurrent intrahepatic cholestasis
Use of oestrogens and steroids
TPN, bacterial infections
Paraneoplastic, syndromes
Intrahepatic cholestasis of pregnancy
postoperative cholestasis

95. DESCRIBE THE LIVER BLOOD SUPPLY ? different factors affecting it?
and
different factors affecting it?

96. 1 2

97. 25% of C.O.- 1500 ml/min, Dual Bld Supply
25% of cardiac output ml/min
30 % BLOOD % BLOOD
40 – 50 % OXYGEN % OXYGEN

98. FACTORS AFFECTING LIVER BLD. SUPPLY
Increased by:
Supine position
Food
Hypercapnia
Acute hepatitis
Drugs: barbiturates, P450 enzyme inducers, b agonists
Decreased by:
Upright position
IPPV/PEEP, Surgery
Hypocapnia, hypoxia
Cirrhosis
Anaesthetics agents
volatile, inhalational, b blockers, a agonists
Surgical Manipulations

99. What are the Functions of Liver ?

100. Protein metabolism – synthesis of plasma pr( albumin & α-acid glcoprotein, C-reactive protein, haptaglobin, pseudocholinestrase, deamination of A.A , formation of urea,
Glucose Homeostasis - gluconeogenesis, glycogenolysis( glucagon), glycogenesis (Insulin)
Fat Metabolism - Synthesis of lipoproteins, cholesterol, triglycerides, oxidation of FA to ketone bodies
Reservoir of Blood
Endocrine Function: IGF1, Thrombopoitin, Angiotensinogen, Thyroid homeostasis, steroid hormone inactivation( Testesterone, estradiol, glucocorticoid, ald.)
Synthesis of all Plasma protein except y globulin & factor VIII including albumin and coagulation factors .

102. Functions of the Liver Bilirubin formation & excretion
Drug & Hormone Metabolism
Phase I & II reactions
Hematological function – haematopoiesis in fetus, heme synthesis,
Immunological function – largest RE organ, Kupffer cells - phagocytosis of Antigen from GIT.
Synthesis of Coagulation factors:I,II,V,VII,IX, X,XI, XII,XIII, prekallikrein,kininogen- Anticoagulants: Antithrombin III, α1antitrypsin, α2 antiplasmin,protein C & S, plasminogen, plasminogen activator inhibitor