Peptic ulcers

A peptic ulcer is an abnormal area of mucosa that has been damaged by the pepsin and hydrochloric
acid of gastric juice, with consequent inflammation of the underlying and surrounding tissue. Most of
peptic ulcer occur either in the duodenum, or in the stomach – Ulcer may also occur in the lower
oesophagus due to reflexing of gastric content – Rarely in certain areas of the small intestine

 Erosion - superficial/partial break within the epithelium or mucosal surface.

 Ulcer - deep break through the full thickness of the epithelium or mucosal surface.

Etiology

Gastric ulcers are found most commonly on the lesser curvature of stomach. Duodenal ulcers
are most common in the first part of the duodenum called the „duodenal cap‟.

 Clinical Features: Burning stomach pain, Feeling of fullness, bloating or belching

Fatty food intolerance, Heartburn, Nausea, Vomiting or vomiting blood — which may appear red or
black, Unexplained weight loss, Appetite changes

Pathogenesis

1. Helicobacter pylori, is a Gram-negative, microaerophilic bacterium (it requires oxygen, but at lower
concentration) usually found in the stomach.

H. pylori predominantly colonise the antrum of the stomach, which is the least acidic. H. pylori also
neutralizes the acid in its environment by producing large amounts of urease, which breaksdown
the urea present in the stomach to carbon dioxide and ammonia. These react with the strong acids
in the environment to produce a neutralized area around H. pylori.

Colonisation of the gastric antrum can lead to persistent low-grade inflammation. This may
damage the epithelial lining leading to the destruction of the normal gastric mucosal

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barrier. This promotes the development of ulcerations and other complications (e.g. upper GI
bleeding, malignancy, gastritis, gastric outlet obstruction).

H. pylori are able to establish themselves within the gastric mucosa because of their ability to
adhere tightly to the epithelium and excrete an arsenal of effector molecules.

2. NSAIDs

NSAIDS inhibition of COX-1 reduces the production of mucosal protective prostaglandins.

NSAIDs are a common cause of GI disturbance (e.g. PUD, gastritis) through their inhibition of
cyclooxygenase-1 (COX-1).

COX-1 is important in the production of prostaglandins. Prostaglandins have a number of

protective effects on the gastric mucosa such as the inhibition of enterochromaffin-like
cells (ECL). This inhibition reduces the secretion of histamine, a hormone that stimulates parietal
cells to secrete hydrochloric acid (HCl).

3. Zollinger-Ellison syndrome is a rare condition in which one or more tumors form in your
pancreas or the upper part of your small intestine (duodenum). These tumors, called gastrinomas,
secrete large amounts of the hormone gastrin, which causes your stomach to produce too much
acid. The excess acid then leads to peptic ulcers, as well as to diarrhea and other symptoms

Cirrhosis
Cirrhosis is a condition in which the liver does not function properly due to long-term damage.[1] This
damage is characterized by the replacement of normal liver tissue by scar tissue.[1] Typically, the disease
develops slowly over months or years.[1] Early on, there are often no symptoms.[1] As the disease
worsens, a person may become tired, weak, itchy, have swelling in the lower legs, develop yellow skin,
bruise easily, have fluid build up in the abdomen.

Etiology

 Hepatotoxicity
Long-standing alcohol abuse (one of the two most common causes of chronic liver disease in the
USA)
Medications (e.g., paracetamol, amiodarone or anticancer drugs such as methotrexate)
Ingesting aflatoxin created by Aspergillus

 Inflammation

 (Chronic) viral hepatitis B, C, and D (see, e.g., “Hepatitis C”) → Chronic hepatitis C is
now the most common cause of cirrhosis in the US.
 Primary biliary cirrhosis (The bile ducts become damaged by an autoimmune process)
 Primary sclerosing cholangitis

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  Autoimmune hepatitis(This disease is caused by an attack of the liver by lymphocytes,)
 Parasitic infections (e.g leishmaniasis, malaria)

 Metabolic disorders

 Non-alcoholic steatohepatitis (NASH) (fat builds up in the liver and eventually causes
scar tissue.)
 Hemochromatosis
 Wilson's disease (Autosomal recessive disorder characterized by low serum
ceruloplasmin and increased hepatic copper content on liver)
 Alpha-1 antitrypsin deficiency
 Hepatic vein congestion or vascular anomalies

Pathophysiology

 Although many factors contribute to the development of cirrhosis, cytokine-mediated

activation of stellate cells has been identified as a central element, as these cells promote
fibrosis, which ultimately leads to cirrhosis.
 Hepatic inflammation → hepatocyte destruction which triggers repair mechanisms →
excess formation of connective tissue (fibrosis) → loss of normal liver function (exocrine
and metabolic)
 Inflammatory cytokines → hepatocyte destruction and stellate cell activation → excess
collagen production → loss of normal liver function (exocrine and metabolic)

Alcoholoic Liver disease

 Alcoholic liver disease is a term that encompasses the liver manifestations of alcohol
overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with
liver fibrosis or cirrhosis.

The mechanism behind this is not completely understood. 80% of alcohol passes through the
liver to be detoxified. Chronic consumption of alcohol results in the secretion of pro-
inflammatory cytokines (TNF-alpha, Interleukin 6 [IL6] and Interleukin 8 [IL8]), oxidative
stress, lipid peroxidation, and acetaldehyde toxicity. These factors cause inflammation, apoptosis
and eventually fibrosis of liver cells.

Alcohol is metabolized by alcohol dehydrogenase (ADH) into acetaldehyde, then further

metabolized by aldehyde dehydrogenase (ALDH) into acetic acid, which is finally oxidized into
carbon dioxide (CO 2) and water (H 2O).

This process generates NADH, and increases the NADH/NAD+ ratio. A higher NADH
concentration induces fatty acid synthesis while a decreased NAD level results in decreased fatty
acid oxidation. Subsequently, the higher levels of fatty acids signal the liver cells to compound it
to glycerol to form triglycerides. These triglycerides accumulate, resulting in fatty liver.

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Definition

Hepatitis refers to an inflammatory condition of the liver. It‟s commonly caused by a viral
infection, but there are other possible causes of hepatitis. These include autoimmune hepatitis
and hepatitis that occurs as a secondary result of medications, drugs, toxins, and alcohol.

Comparision of different Viral Hepatitis

Pathophysiology Hepatitis A, B, C ,D, and E

Hepatitis A is a non-enveloped single-stranded ribonucleic acid (RNA) virus classified as the

Hepatovirus genus under the Picornaviridae family. The only host for the HAV is humans, with
hepatic cells as the primary site for viral replication. As part of the viral degradation process, the
HAV is Released into the biliary system, causing elevated concentrations of the virus in the
feces.

Hepatitis B (also known as the Dane particle) belongs to the Hepadnaviridae family that was first
discovered by associating individuals who developed hepatitis from blood transfusions. The
HBV is unique in that it is a partially double-stranded deoxyribonucleic acid (DNA) virus with a
phospholipid layer containing hepatitis B surface antigen (HBsAg) that surrounds the
nucleocapsid. The nucleocapsid contains the core protein that produces hepatitis B core antigen
(HBcAg), which is undetectable in the serum. The exact mechanism of hepatocellular injury
from hepatitis B is still being investigated but it is thought that a cytotoxic immune reaction
occurs when HBcAg is expressed on the surface of the hepatic cells. Fortunately, antibodies
against hepatitis B core antigen (anti-HBc) are measurable in the blood, where anti-HBc to
immunoglobulin M (IgM) indicates active infection and anti-HBc to IgG relates to either chronic
infection or possible immunity against HBV. Viral replication occurs when hepatitis B envelope

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antigen (HBeAg) is present and circulating in the blood. HBV DNA is utilized to measure viral
infectivity and assess and quantify viral replication. Once the hepatitis B infection resolves,
antibodies against hepatitis B envelope (anti-HBe) and antibodies against hepatitis B surface
antigen (anti-HBs) develop, and HBV DNA levels become undetectable. However,if these
antibodies do not develop, then the likelihood of developing chronic hepatitis B increases. This is
primarily dependent on the host‟s immune system at the time the infection was attained. If an
individual is immunocompetent, the disease resolves spontaneously in most cases with no further
sequelae.

Hepatitis C, first known as non-A, non-B hepatitis, is a blood borne infection that is a single-
stranded RNA virus belonging to the Flaviviridae family and the Hepacivirus genus. The true
mechanism of hepatic injury is still in question, but it is theorized that structural and
nonstructural (NS) peptides may be responsible for RNA viral replication, specifically the NS5
peptide. Antibodies against HCV (anti-HCV) in the blood indicate infection with the HCV. If the
infection persists for more than 6 months and viral replication is confirmed by HCV RNA
levels, then the person has chronic hepatitis C. Chronic disease may be due to an ineffective host
immune system against the HCV.Cytotoxic T lymphocytes are ineffective in eradicating the
HCV, thus allowing persistent damage to hepatic cells. Therefore, immunocompromised
individuals are less likely to eliminate HCV.

Hepatitis D (originally referred to as delta hepatitis) belongs to the genus Deltavirus of the
Deltaviridae family.The HDV virion is a defective single-stranded circular RNA virus that
requires the presence of HBV for HDV viral replication. This is because the hepatitis D virus
antigen (HDVAg) is coated by the hepatitis B surface antigen (HBsAg). The exact mechanism of
hepatic damage induced by HDV Is still being investigated, but it is known that replication of
HDV cannot occur without HBV being present causing either co-infection (both hepatitis B and
D infection occurring simultaneously) or superinfection (acquiring HDV after having long-
standing disease with HBV).

Hepatitis E is a non-enveloped single-stranded messenger RNA virus of unclassified genus.18

The HEV is similar to HAV in that the virus is harvested in contaminated feces, thus infecting
people via the fecal-oral route. High HEV levels in the bile often prompt viral shedding in the
feces. The severity of hepatic damage is dependent on the HEV strain: Mex 14, Sar 55, or the US
2 strain.