The document discusses the anatomy, histology, functions and common pathologies of the liver. Key points include:
- The liver has four lobes and receives dual blood supply from the hepatic artery and portal vein. It performs many metabolic and synthetic functions.
- Common liver diseases include viral hepatitis, alcoholic liver disease and cirrhosis. Cirrhosis results from chronic liver injury and scarring that disrupts the liver architecture.
- Primary liver cancers like hepatocellular carcinoma often arise in the setting of chronic liver disease and cirrhosis. Treatment options are limited but may include transplantation or resection in early stages.
3. The Liver
The right upper quadrant of the abdomen is
dominated by the liver and its companion
biliary tree and gallbladder.
Residing at the crossroads between the
digestive tract and the rest of the body, the
liver has the enormous task of maintaining the
body's metabolic homeostasis.
6. Sheets of connective tissue divide the liver into
thousands of small units called lobules.
The lobule is the structural unit of the liver, with
portal triads at the vertices and a central vein in
the middle.
The parenchymal cells of the liver are
Hepatocytes
Hepatocytes make contact with blood in
sinusoids
10. Liver Functions:
Metabolism – Carbohydrate, Fat & Protein
Secretory – bile, Bile acids, salts & pigments
Excretory – Bilirubin, drugs, toxins
Synthesis – Albumin, coagulation factors
Storage – Vitamins, carbohydrates etc.
Detoxification – toxins, ammonia, etc.
11. Hepatitis:
Hepatitis: Inflammation of Liver
Viral, Alcohol, immune, Drugs & Toxins
Biliary obstruction – gall stones.
Specific – Heptitis A, B, C, D, E, & other
12. Transmission
Hepatitis A and E are typically caused by
ingestion of contaminated food or water.
Hepatitis B, C and D usually occur as a result
of parenteral contact with infected body fluids.
Like contaminated blood or blood products,
semen, invasive medical procedures using
contaminated equipment, drug abuse
Hepatitis B transmission from mother to baby
at birth.
13.
14.
15. Pattern of Viral Hepatitis:
Carrier state / Asymptomatic phase
Acute hepatitis
Chronic Hepatitis
Chronic Persistent Hepatitis (CPH)
Chronic Active Hepatitis (CAH)
Fulminant hepatitis
Cirrhosis
Hepatocellular Carcinoma
16. Acute Hepatitis:
Swelling and Apoptosis
Piecemeal or Bridging, panacinar necrosis
Inflammation – lymphocytes, Macrophages
Ground glass hepatocytes – HBV
Mild fatty change – HCV
Portal inflammation and Cholestasis
17. Foreign bodies, organisms, and a variety of drugs may incite
a granulomatous reaction.
23. Signs and Symptoms
Abdominal pain
Joint and muscle pain
Change in bowel function
Nausea, vomiting, anorexia
Lethargy, malaise
Fever (Hepatitis A)
Irritability
24. More Signs and Symptoms
oJaundice
oclay colored stools
odark urine
oPruritis/urticaria
oSkin abrasions
oRash
25. Fulminant Hepatitis:
Hepatic failure with in 2-3 weeks.
Reactivation of chronic or acute hepatitis
Massive necrosis, shrinkage, wrinkled
Collapsed reticulin network
Only portal tracts visible
Little or massive inflammation – time
More than a week – regenerative activity
Complete recovery – or - cirrhosis.
27. Hepatocyte necrosis is distributed
immediately around the central vein
(centrilobular necrosis).
Destruction of entire lobules (submassive
necrosis) or most of the liver parenchyma
(massive necrosis) is usually accompanied
by hepatic failure.
30. C
LESS common than B (one fourth)
LESS dangerous than B in the acute phase
MORE likely to go chronic than B
MORE closely linked with hepatoma than B
31. Jaundice
Yellow discoloration of sclera, skin, mucous
membranes due to deposition of bile pigment
Clinically detected with serum bilirubin 2-
2.5mcg/dL or ↑ (2 times nl)
32. Common Causes of Jaundice
Pre Hepatic (Acholuric) - Hemolytic
Unconjugated/Indirect Bil, pale urine
Hepatic – Viral, alcohol, toxins, drugs
Liver damage - unconjugated
Swelling, canalicular obstruction - Conjugated
Post Hepatic (Obstructive) – Stone, tumor
Conjugated/Direct Bil, High colored urine,
33. Normal bilirubin production
(0.2 to 0.3 g/day) is derived
primarily from the breakdown
of erythrocytes.
Extrahepatic bilirubin is
bound to serum albumin and
delivered to the liver.
Bilirubin Metabolism And
Elimination.
34. (1) excessive production of bilirubin, (2) reduced hepatic
uptake,
(3) impaired conjugation, (4) decreased hepatocellular
excretion, and
(5) impaired bile flow (both intrahepatic and
extrahepatic).
The first three mechanisms produce unconjugated
hyperbilirubinemia, and the latter two produce predominantly
conjugated hyperbilirubinemia.
35.
36. PATHOPHYSIOLOGY OF
JAUNDICE
This un-conjugated bilirubin may
accumulate systemically and deposit in
tissues, giving rise to the yellow
discoloration of jaundice.
This is particularly evident in the
yellowing of the sclerae (icterus).
Un-conjugated bilirubin is tightly
complexed to serum albumin and is
virtually insoluble in water at
physiologic pH.
37. This form cannot be excreted in
the urine even when blood levels
are high.
In contrast, conjugated bilirubin
is water soluble, nontoxic, and
only loosely bound to albumin.
40. Jaundice is an almost invariable finding.
Impaired hepatic synthesis and secretion of albumin leads
to hypoalbuminemia, which predisposes to peripheral edema.
Hyperammonemia is attributable to defective hepatic urea
cycle function.
Fetor hepaticus is a characteristic body odor variously
described as "musty" or "sweet and sour" and occurs
occasionally.
Clinical Features
41. A coagulopathy develops, attributable to impaired hepatic
synthesis of blood clotting factors II, VII, IX, and X.
The resultant bleeding tendency may lead to massive
gastrointestinal hemorrhage as well as petechial bleeding
elsewhere.
Hepatic encephalopathy
Hepatic encephalopathy is a feared complication of acute
and chronic liver failure
42. Cirrhosis
Cirrhosis is a pathologically defined entity that is
associated with a spectrum of characteristic clininical
manifestation
1.Irreversible chronic injury of the hepatic
parenchyma
2.Extensive fibrosis
3.Formation of regenerative nodules
46. Cirrhosis: Pathophysiology
Primary event is injury to hepatocellular elements
Initiates inflammatory response with cytokine
release->toxic substances
Destruction of hepatocytes, bile duct cells,
vascular endothelial cells
Repair thru cellular proliferation and regeneration
Formation of fibrous scar
47. Cirrhosis: Pathophysiology
The normal liver contains interstitial collagens (types I, III,
and IV) in portal tracts and around central veins, with
occasional bundles in the parenchyma.
Primary cell responsible for fibrosis is stellate cell
Become activated in response to injury and lead to ↑ed
expression of fibril-forming collagen
Above process is influenced by Kupffer cells which activate
stellate cells by eliciting production of cytokines
Sinusoidal fenestrations are obliterated because of ↑ed
collagen and EC matrix synthesis
48. Cirrhosis: Pathophysiology
Portal vein-to-hepatic vein and hepatic artery-to-
portal vein vascular shunts also develop.
Prevents normal flow of nutrients to hepatocytes
and increases vascular resistance
Initially, fibrosis may be reversible if inciting events
are removed
With sustained injury, process of fibrosis becomes
irreversible and leads to cirrhosis
49. Pathogenesis
Hepatocyte injury leading to necrosis.
Alcohol, virus, drugs, toxins, genetic etc..
Chronic inflammation - (hepatitis).
Bridging fibrosis.
Regeneration of remaining hepatocytes
Proliferate as round nodules.
Loss of vascular arrangement results in
regenerating hepatocytes ineffective.
62. Prevention Teaching
What would you teach?
• Adequate sanitation and hygiene
• Wash hands before eating and after
using the toilet
• Drink only purified or bottled water
• No sharing of eating utensils,
needles, toothbrushes, razors, etc.
• Choose your tattoo or piercing
person carefully. Inspect the facility
68. Pathogenesis
Several factors relevant to the pathogenesis of HCC.
Three major etiologic associations have been established:
infection with HBV, chronic liver disease.
Many factors, including age, sex, chemicals, viruses,
hormones, alcohol, and nutrition, interact in the
development of HCC.
The development of cirrhosis appears to be an important,
but not requisite, contributor to the emergence of HCC.
69. Treatment
Liver transplatation
Surgical resection (best prognosis for
long-term survival, but possible in only
10-15% of cases)
Radiotherapy
Editor's Notes
b
The classical view of liver tissue from a liver biopsy, H&E stained.
Bowel function: either new onset of diarrhea or constipation
Abdominal pain – also liver tenderness
RUQ pain with any jarring motion
Fever with hep A, usually low grade with or absent with B and C
Jaundice due to intrahepatic obstruction from edema of liver’s bile channels
Consequences of hepatitis B, surprisingly, most cases of Hepatitis B are SUB-clinical
Consequences of hepatitis C
Hepatocytes have “feathery” cytoplasm
How would the blind man know this is metastatic cancer, rather than macronodular cirrhosis?