Dr.

Darli

Hepatocyte injury by
virus, alcohol or drug
Ballooning, fatty change
apoptosis or necrosis with
variable distribution

1
Vascular disease,
congestion, infarction

hepatocyte

CPVC

Inflammation,
lymphocyte,
neutrophil, granuloma
Regeneration,

cv

fibrosis

Cirrhosis and?
cancer
Gall bladder

RBC

conjugation

N
Ito

excretion

5,6

PARASITES AND TUMOURS

Portal & hepatic

sinusoid

AVD

1.Chronic passive venous congestion of the liver CPVC

Constrictive pericarditis, CCF are main causes for back pressure

CV are congested and centrilobular necrosis occur.
Periportal region: relatively less ischemia compare to the hepatocytes.
Alternate red color due to congestion and pale color due to fat give
nutmeg appearance
Long standing cases end up in cardiac cirrhosis
can be the reason for nonspecific symptoms like flatulence,indigestion
and right hypochondrial discomfort

5. Cirrhosis of the liver

One of the top 10 causes of death in the western world.
It is characterized by:
1. hepatocyte injury of many causes.
2. regeneration of remaining cells to form nodules.
3. fibrosis replacing the damaged tissue.
4. loss of global architecture because of the whole process.
5. reorganised vascular architecture resulting in shunts

Causes of the cirrhosis

1.
Alcoholic 60-70%
2.
Post viral infection-HBV 10%
3.
Biliary 5-10%
4.
Haemochromatosis 5%
5.
Wilsons disease, alfa-1 AT deficiency
6.
Cryptogenic (no known cause) 10-15%
7.
Others: galactosemia, cardiac, syphilis.

Pathogenesis***

Extensive fibrosis with type I and III collagen synthesis in the

lobules
Cells of Ito are the source of collagen. They are stimulated by
TNF-, TGF , IL, destruction of extracellular matrix and toxins.
Remaining cells regenerate into irregular nodules.
Fibrosis and nodule formation results in disorganization of
sinusoids, they become like capillaries and hepatocyte isolation
resulting in decreased secretion of albumin, clotting proteins and
lipoproteins. anastomosis results in high pressure in capillaries and
establishment of shunts.
Bile duct obliteration results in jaundice.
Increased HP, hypoalbuminemia, increased thoracic duct flow,
osmotic effects, sodium retention all lead to ascitis and edema.
congestion leads to splenomegaly.

Point of no return

1. necrosis.
2. regeneration->nodule.

3. fibrosis.
3

4. vascular change

Macronodular cirrhosis

Hepatic failure
80-90% cell destruction- loss of function
VH, drugs: INH, acetaminophen, mushroom,

alcohol are some of the causes

GI bleed, infection, electrolyte disturbance,
surgery, CCF hasten failure
C/F: Jaundice, hypoalbuminemia,
hyperammonemia, fetor hepaticus, palmar
erythema, spider nevii. hypogonadism,
gynecomastia, ARDS, uremia, coagulopathy,
encephalopathy, hepatorenal syndrome and
multi organ failure.

Jaundice

Yellow discoloration of skin & sclera due to

excess serum bilirubin. >40umol/l,

(3mg/dl)
Conjugated & Unconjugated types
Obstructive & Non Obstructive (clinical)
Pre-Hepatic, Hepatic & Post Hepatic types
Jaundice - Not necessarily liver disease *

Ascites in Cirrhosis

Porta-systemic anastomosis:
Prominent abdominal veins.
Gynaecomastia in cirrhosis

Pathophysiology of portal
hypertension

Edema

hypoalbuminaemia

Ascites
Secondary aldosteronism
Portal hypertension
Hypoalbuminemia

Hematemesisrupture esophageal

varices due to portal

hypertension
Spidernaevihyperestrogenism
Purpura and bleedreduced clotting factors
Coma- bacterial
metabolites
Infection- reduced Kupffer
cell no. and function

Blood:
Conjugated & Unconjugated

Urine Urobilinogen

Stool Stercobilin

Causes of PHT

Pathogenesis of portal H

Pre- sinusoidal
Portal fibrosis due to
Sarcoidosis
Schistosomiasis
Hepatoportal sclerosis
Cirrhosis

Sinusoidal
Cirrhosis

Post- sinusoidal
Budd-Chiari

syndrome
(Thrombosis of
hepatic veins)
Tumors

Hemodynamic

changes
proximal or distal to
sinusoids or at sinusoid.

Increased

portal
vascular resistance and
intrahepatic shunting
between high pressure
hepatic artery and portal
veins

Primary carcinoma liver

Can be hepatocellular (90%) /cholangiocarcinoma

(10%)
Most common visceral cancer
In developing countries vertical transmission of
infection from mother to baby leading to carrier
state and cancer occurs around 40yr
In developed countries after 60yrs because of
cirrhosis due to HCV or alcohol or hemochromatosis

Pathogenesis.
HBV virion integrates and as regeneration

occurs mutations take place.

protein X is produced
It has insulin GF-property and binds to p53
resulting in its growth suppressor activity.
Aflotoxins in some food integrate with liver cell
DNA and mutating p53,(in subsaharan Africa
and china genetically people may lack enzymes
for detoxifying aflotoxins)
Cirrhosis due to HCV or alcohol

Morphology.
Gross.
as unifocal nodule, multifocal
nodule or diffusely infiltrative
type.
All cause liver enlargement
Nodule may look pale or greenish
Invasion of tumour to portal
vein/IVF seen
Microscopy.
pattern varies from well
differentiated to highly anaplastic
Trabecular, acinar,
pseudoglandular patterns can
occur.
Features of anaplasia, inreased
N:C ratio, nucleoli and
intranuclear inclusions.

SECONDARY TUMOURS
Metastasis to liver from other organs is more

common than primary

Metastasis from cancer anywhere in the body
can be found in liver. Most from breast, lung,
colon and stomach ca
Liver is enlarged, nodular with umbilication
They can be asymptomatic.

Liver cysts
Simple cyst / Polycystic disease
Small multiple cyts (10-20mm)

Hydatid cysts
Echinococcus granulosus
Lamainated fibrous wall
Numerous daughter cysts-rupture-

anaphylactic shock in sensitized patients

Choledocheal cysts
Rare, intra or extrahepatic cysts of bile ducts
Predispose to cholangitis

Acute
pancreatitis
Autodigestion of the pancreas by its escaped
enzymes

Clinical features
(Symptoms)
1. Pain
(sudden,intense,continuous,
upper abdomen back,
bizarre position)
Investigations:
2.

1-Blood tests

Nausea and Vomiting

Serum amylase and lipase levels may be
slightly elevated in chronic pancreatitis;
high levels are found only during acute
attacks of pancreatitis.

-Abdominal x-ray:
Pancreatic calcifications, often considered
pathognomonic of chronic pancreatitis, are observed
in approximately 30% of cases.

Etiology: (GET SMASHED)

G: Gallstone.(common)
E: Ethanol.
T: Truma..
S: Steroid..
M: Mumps.
A: Alcoholism (common) or autoimmune.
S: Scorpion bits.
H: Hyperlipidemia.
E: ERCP.
D: Drugs: Thiazide,

Azathioprine.

 When the activation of digestive proenzymes occurs in

Pathophysiology:
pancreatic duct system or aciner cells, the

inflammation is the result.

Oedema or obstruction of ampulla of veter resulting in
reflexes Of bile into pancreatic duct or to acinar cells.
Pancreas shows edema & necrosis.(10%-30% mortality
rate).
The release of digestive enzymes lead to fat necrosis in
the pancreas &peritoneal cavity.
DDx:

Perforated peptic ulcer.

Acute cholecystitis & biliary colic.
Acute Int obstruction.
Renal colic.
DKA.

Clinical Features:
Hx :
Abdomenal pain:

sever, stay 12-24h after eating a large meal or

consuming alcohol,rediate to the back or to the
shoulder, pain is worse by walking or laying supine &
better after sitting or leaning forward.
N &V.
Shock in sever case.
Severe acute pancreatitis may cause dehydration and
low blood pressure. The heart, lungs, or kidneys can
fail. If bleeding occurs in the pancreas, shock and
even death may follow.
Abd Ex:
Tenderness in epigastric & guarding of Abd
muscles.
Mild Abd distention( if the purulytic ileus develop).
In sever advanced case:
1.Grey turners sign.

Investigation:
Serum amylase;
It stays 48-72h then become normal.
Serum lipase; (diagnostic test)
It elevated for 7-14 days.
Other:
-WBC (15000-30000).
-LDH>500
U/dl
- Glucose.
- Albumin.
- Ca in serum.
- AST.Bilurbin,Alkaline Ph.
- ABG show Hypoxia.

 Xray of Abdomen:

-gall stones.
-Sentinel loop: air filled SI in the LUQ.
-Colon cut off sign: gas-filled seg of transverous colon
abruptly ending at the area of pancreatic inflammation.

U/S:

-Gall stones.
-Bilary obstruction.
-Psudocyst.

 CT:

(is the dignostic even with normal amylase).

-enlarged pancreas.
-Psudocyst.
-Abscess & hemorrhage.
-Presence of gas bubbles in CT scan indicate pancreatic
abscess.

COMPLICATION

3.

Shock & renal failure:(pancritic necrosis is

association with leakage of fluid in the pancreatic bed
& also illus with fluid filled the bowl leading to tubular
necrosis).
Hypo Ca: sequestration of Ca in fat necrosis.
(sponification)
Hypoalbuminemia: Capillary permeability.

4.

Hyperglucemia: due to disruption of pancreatic

1.

2.

islets.
5.

Hypoxia: Resp distress.

6- Pancreatic :
-Necrosis.
-Abscess.
-Pseudocystis:
a circumscribed collection of fluid rich in pancreatic
enzymes, blood, and necrotic tissue, typically
located in the lesser sac of the abdomen. Pancreatic
pseudocysts are usually complications of
pncreatitis. The prefix pseudo- (Greek for "false")
distinguishes them from true cysts, which are lined
by epithelium; pseudocysts are lined with
granulation tissues.
7- GI: -UGI Bleeding. -duodenal obstruction.
-Gastric or duodenal erosion.
-splenic or portal vein thrombosis.
- compression by pancreatic mass.
- compression of common bile duct.

Assesment of severity
(Ransons
Criteria)

3 or more indicate sever pancreatitis:

1.Age > 55 Y/O.
2.Blood glucose > 200 mg/dl.
3.WBC > 16000
4.AST > 250 IU/L.
5.Serum LDH >350 IU/L.

Development of the following in the

first 48h indicate a worsening porgnosis:
(PANCREAS)
P:
A:
N:
C:
R:
E:

PO2 < 8KPa.

Age > 55y.
Neutrophil > 15000000000L.
Calcium <2 mmol.
Renal function. (Urea> 16 mmol/L)
Enzymes: -LDH>600 iu/L.
-AST >200 iu/L.
A: Albumin:<32 g/L in serum.
S: Sugar > 10 mm0l/L.

Chronic Pancreatitis:
Is chronic inflammatory disease characterized by fibrosis & dustruction of

exocraine pancreatic tissues.

Both forms of pancreatitis occur more often in men than women.
Chronic pancreatitis often develops in people who are between the ages of
30 and 40.

Etiology
Alcoholism.(common)
Malnutrition.
Stnosis of ampulla of veter.

C/F:
Abd pain.
2. Weight loss, Aneroxia, Avoidness of food bcz of postprandial pain, Malabsorbtion.
3. Steatorrhea.
4. On Ex:
Investigation
Epigastric pain.
1.

Abd xray : clacified pancreas.

U/S Abd
CT Abd: : atrophy,clacification.
ERCP.

What
is Pancreatic
Cancer
A disease
in which malignant
(cancer) cells are found in the
tissues of the pancreas
4th leading cause of death from cancer in males
5th in females
Affects people at 70-80 y/o
60-80% occur at the head of the pancreas

Laboratory
Tests
BLOOD TESTS:
Amylase: (normal value: 30-110 U/L) the blood level of amylase is usually

significantly elevated
>>Critical value: <250 U/L
Comprehensive metabolic panel: may reveal elevated bilirubin and

alkaline phosphatase
>>Normal values: bilirubin= 0.2-1.3 mg/dl , phosphatase= 38-126 U/L
>>8-12 hours fasting for more accurate results

CEA (Carcinoembryonic
antigen): a tumor marker used
as a monitoring tool
Normal Value: <2.5 ng/mL in an
adult non-smoker and <5.0

 CA 19-9 (Cancer Antigen 19-9) testing: Cancer antigen 19-9 (CA 19-9) is

a protein that exists on the surface of certain cancer cells.

>>a tumor marker for pancreatic cancer; it may be used to monitor for
cancer recurrence but is not useful for detection or diagnosis
>>Normal Value: <40 U/mL
>>CA 19-9 >37 U/mL result may indicate pancreatic cancer
>>CA 19-9 is elevated in about 70% of people with advanced pancreatic
cancer

Computed tomography (CT)

scan: useful for detecting
pancreatic masses and
checking for metastasized
cancer
Biopsy: used to confirm
diagnosis of cancer, often in
conjunction with CT scan.

The primary filtering element for the blood. Acts as

a filter against foreign organisms that infect the
blood stream.
The site of red blood cell and platelet storage.
Filters out old red blood cells and recycles them.

TUMORS
Spleen - mostly secondary involvement
non-Hodgkins Lymphoma most common malignancy
Main Tx: Chemo +/- RT

Spleen is the primary site

10% Hodgkins disease
30% of resected spleens (staging procedure) have (+) histology

Hairy cell leukemia

Resect for symptomatic splenomegaly

Improved survival

CML & CLL

symptomatic splenomegaly = splenectomy