Your instructorwill assign you a disease topic for your papers( Liver Disease). Your references MUST
include at least 5 recent primary research articles, 3 of which are from journals published by the
American Physiological Society (APS). There are 7 American Journal of Physiology (AJP) journals to
choose from: Cell Physiology; Endocrinology & Metabolism; Gastrointestinal & Liver Physiology; Heart &
Circulatory Physiology; Lung, Cellular & Molecular Physiology; Regulatory, Integrative & Comparative
Physiology; and Renal Physiology. In addition, there are a few other journals published by the APS that
include primary research that can be found
Writing the papers:
Paper 1
Start the body of the paper on a new page after the title page. A minimum of 10 references are required
and the paper should be 5 pages long. You are required to review the pathophysiology of the disease
using these headings;
Introduction
Epidemiology
Etiology
Types/ Classification
Normal Physiology and Homeostasis
Pathophysiology and Molecular Basis of the Disease
Signs/ Symptoms
Laboratory Features
Differential Diagnosis
Complications and Prognosis
BIOM 525
PAPER INSTRUCTIONS
Paper Topic:
Your instructor will assign you a disease topic for your papers. Your references MUST include at least 5
recent primary research articles, 3 of which are from journals published by the American Physiological
Society (APS). There are 7 American Journal of Physiology (AJP) journals to choose from: Cell
Physiology; Endocrinology & Metabolism; Gastrointestinal & Liver Physiology; Heart & Circulatory
Physiology; Lung, Cellular & Molecular Physiology; Regulatory, Integrative & Comparative Physiology;
and Renal Physiology. In addition, there are a few other journals published by the APS that include
primary research that can be found here.
Writing the papers:
Paper 1
Start the body of the paper on a new page after the title page. A minimum of 10 references are required
and the paper should be 5 pages long. You are required to review the pathophysiology of the disease using
these headings;
- Introduction
- Epidemiology
- Etiology
- Types/ Classification
- Normal Physiology and Homeostasis
- Pathophysiology and Molecular Basis of the Disease
- Signs/ Symptoms
- Laboratory Features
- Differential Diagnosis
- Complications and Prognosis
Paper 2
Start the body of the paper on a new page after the title page. You should review current research on at
least five (5) pharmacological management options for the disease (from paper 1) including drugs in
clinical trials. Your review should include these components:
1) The physiologic rationale for using the drugs in treating your assigned disease.
2) The mechanisms of action of these drugs.
3) The side effects of these drugs and their contraindications.
4) The dosages and routes of administration of the drugs.
This section must include a minimum of 5 unique references that are recent and the paper should be 3
pages long.
Figures
Figures are allowed in any section, but do not count towards page count. These can be your original
figures/drawings or (if properly cited) from one of your sources. Place all figures at the end of the paper.
BIOM 525
Formatting the paper:
1) Student’s name must not appear anywhere on title page, paper, file name, or comments.
2) The title page for each paper should include the title of the entire project; course name, number,
and section number; professor’s name; and date. Title page does not count toward the page count.
3) Paper must be double-spaced, including between paragraphs. New paragraphs should be started
with a single tab.
4) Paper must have 1” margins on all sides.
5) Font must be 12 pt., Arial font (regular).
6) Minimum lengths refer to full pages; a full page is 23 lines of text. Do not use section headings for
“filler” as these will not count towards page count. Short or long papers will be penalized based on
the amount written/missing.
7) Direct quotations are not appropriate for this project; you are to write a paper, not copy and paste
from other papers.
8) All references must be professional peer-reviewed articles.
9) Your in-text citations and references need to be in current American Journal of Physiology – Cell
Physiology format. There is an EndNote template for this style; it is highly suggested that you use
it as you start doing research.
Failure to follow any of these formatting instructions will result in loss of points. (See rubrics.)
Each section will be graded on clarity and demonstration of mastery of topic. The information must be
accurate, and the writing must indicate thorough graduate-level work. The writing level and style should
be the same as the peer-reviewed professional articles you use for your sources.
Please review the Academic Honor Code to ensure you are following it when writing the paper. Penalties
for Academic Dishonesty can include failure of the assignment or the entire course.
Submitting the paper:
Each paper must be submitted to SafeAssign and must match fewer than 15%. (See rubrics.)
Paper 1 is due by 11:59 p.m. (ET) on Sunday of Module/Week 4.
Paper 2 is due by 11:59 p.m. (ET) on Sunday of Module/Week 6.
BIOM 525
PAPER INSTRUCTIONS
Paper Topic:
Your instructor will assign you a disease topic for your papers. Your references MUST include at least 5
recent primary research articles, 3 of which are from journals published by the American Physiological
Society (APS). There are 7 American Journal of Physiology (AJP) journals to choose from: Cell
Physiology; Endocrinology & Metabolism; Gastrointestinal & Liver Physiology; Heart & Circulatory
Physiology; Lung, Cellular & Molecular Physiology; Regulatory, Integrative & Comparative Physiology;
and Renal Physiology. In addition, there are a few other journals published by the APS that include
primary research that can be found here.
Writing the papers:
Paper 1
Start the body of the paper on a new page after the title page. A minimum of 10 references are required
and the paper should be 5 pages long. You are required to review the pathophysiology of the disease using
these headings;
- Introduction
- Epidemiology
- Etiology
- Types/ Classification
- Normal Physiology and Homeostasis
- Pathophysiology and Molecular Basis of the Disease
- Signs/ Symptoms
- Laboratory Features
- Differential Diagnosis
- Complications and Prognosis
Paper 2
Start the body of the paper on a new page after the title page. You should review current research on at
least five (5) pharmacological management options for the disease (from paper 1) including drugs in
clinical trials. Your review should include these components:
1) The physiologic rationale for using the drugs in treating your assigned disease.
2) The mechanisms of action of these drugs.
3) The side effects of these drugs and their contraindications.
4) The dosages and routes of administration of the drugs.
This section must include a minimum of 5 unique references that are recent and the paper should be 3
pages long.
Figures
Figures are allowed in any section, but do not count towards page count. These can be your original
figures/drawings or (if properly cited) from one of your sources. Place all figures at the end of the paper.
BIOM 525
Formatting the paper:
1) Student’s name must not appear anywhere on title page, paper, file name, or comments.
2) The title page for each paper should include the title of the entire project; course name, number,
and section number; professor’s name; and date. Title page does not count toward the page count.
3) Paper must be double-spaced, including between paragraphs. New paragraphs should be started
with a single tab.
4) Paper must have 1” margins on all sides.
5) Font must be 12 pt., Arial font (regular).
6) Minimum lengths refer to full pages; a full page is 23 lines of text. Do not use section headings for
“filler” as these will not count towards page count. Short or long papers will be penalized based on
the amount written/missing.
7) Direct quotations are not appropriate for this project; you are to write a paper, not copy and paste
from other papers.
8) All references must be professional peer-reviewed articles.
9) Your in-text citations and references need to be in current American Journal of Physiology – Cell
Physiology format. There is an EndNote template for this style; it is highly suggested that you use
it as you start doing research.
Failure to follow any of these formatting instructions will result in loss of points. (See rubrics.)
Each section will be graded on clarity and demonstration of mastery of topic. The information must be
accurate, and the writing must indicate thorough graduate-level work. The writing level and style should
be the same as the peer-reviewed professional articles you use for your sources.
Please review the Academic Honor Code to ensure you are following it when writing the paper. Penalties
for Academic Dishonesty can include failure of the assignment or the entire course.
Submitting the paper:
Each paper must be submitted to SafeAssign and must match fewer than 15%. (See rubrics.)
Paper 1 is due by 11:59 p.m. (ET) on Sunday of Module/Week 4.
Paper 2 is due by 11:59 p.m. (ET) on Sunday of Module/Week 6.
1
Pathophysiology of Liver Disease
Name
Institutional Affiliation
Course
Instructor
Date
2
Pathophysiology of Liver Disease
Approximately one-third of American adults have been diagnosed with chronic
hepatobiliary disease. The multiple etiologies include alcoholic liver disease, autoimmune liver
diseases, non-alcohol liver disease, metabolic diseases and drug-induced liver injury. Liver
disease can be chronic or acute, mild or severe, focal or diffuse, and reversible or irreversible.
For obstetrician-gynaecologists to conduct specialized care for adults and adolescents, there is a
need for understanding the basics of liver physiology and anatomy, the significance of abnormal
levels of serum bilirubin and abnormal liver test results, and strategies for imaging and additional
testing required for diagnosis (Gual et al., 2017). Consequently, early therapy and diagnosis
provide the best hope for combating the progression of hepatobiliary diseases to liver failure,
cirrhosis and the need for liver transplantation. Therefore, this paper review the pathophysiology
of liver disease in terms of epidemiology, etiology, classification, normal physiology and
homeostasis, pathophysiology and molecular basis of liver disease, symptoms, laboratory
features, differential diagnosis, and complications and prognosis.
After reviewing the prevalence, incidence, and mortality of chronic liver disease (CLD),
it is discerned that nearly 1.5 billion people are suffering from CLD worldwide; at the same time,
cirrhosis mortality and prevalence have risen in the United States (Rowe, 2017). As a result, the
epidemiology of CLD is reflecting the execution of large scale hepatitis C treatment programs
and hepatitis B vaccination, increasing alcohol misuse and the increasing prevalence of
metabolic syndrome. Since 1990, cirrhosis has become a major threat to health due to ageing and
population growth. The majority of liver-related death globally have been attributed to cirrhosis;
it is usually compensated at the initial stages since liver cirrhosis is incidentally discovered
during medical tests for other reasons (Rowe, 2017). Despite chronic infection with alcoholic
3
liver disease (ALD) and hepatitis C virus (HCV) being the major cause of CLD in the United
States, non-alcoholic fatty liver disease (NAFLD) has taken over as the major cause. According
to the United Network for Organ Sharing statistic, the percentage of new waitlist liver transplant
registrants is as follows: ALD increased by 45%, NAFLD increased by 170 %, while HCV
increased by 45 %.
The etiology of liver disease is diverse; however, the common causes include infections,
immune system problems, cancer and other growths, genetics inheritance alongside other causes.
Similarly, it is through these causes that the types of liver diseases are identified. Concisely, the
cause of infections is attributed to liver inflammation; this includes viral hepatitis such as
Hepatitis A, Hepatitis B and Hepatitis C. Hepatitis A is caused by drinking or eating foodstuffs
that are polluted by fecal matter; Hepatitis B is transmitted through unprotected sex and sharing
of drug needles; while Hepatitis C is acquired through the transmission of infected blood
(Godfrey et al., 2019). Additionally, immune system problems may cause liver disease due to the
invasion of viruses and bacteria that attack the liver; this includes autoimmune hepatitis, primary
sclerosing cholangitis, and primary biliary cholangitis. Autoimmune hepatitis cause liver failure
through inflammation and is most prevalent in women and girls than male counterparts; primary
biliary cholangitis attacks bile ducts in the liver backing up the bile, thus scaring it; and primary
sclerosing cholangitis block the bile ducts making it harder for the liver to function. Few cancers
and growth can start in the liver, thus causing liver disease; this includes liver cancer, bile duct
cancer, and liver cell adenoma. According to Godfrey et al. ( 2019), liver cancer is attributed to
excessive alcohol consumption; bile duct cancer attacks the tube carrying bile from liver to small
intestine; liver cell adenoma is a tumor usually affects woman with high intake of birth control
pills. Eventually, genetics causes liver disease through inherited liver disorders running in the
4
family; this includes hemochromatosis, hyperoxaluria, Wilson's disease and alpha-1 antitrypsin
deficiency. Hemochromatosis causes the building up of the iron in the liver, thus causing liver
disease; hyperoxaluria is caused by high levels of oxalate in the urine due to genetic mutation
causing the liver to make much oxalate; Wilson's disease is caused by copper building up in the
liver hence affecting it; ultimately, alpha-1 antitrypsin deficiency involves a chemical protecting
the lungs against invention, but when the liver gets it wrong it builds up causing liver disease
(Bataller et al., 2015). Other causes of liver disease include alcohol abuse that causes liver
cirrhosis, and non-alcoholic fatty liver disease resulting from fats building up in the liver.
In describing the normal physiology and homeostasis of liver disease, the liver forms an
essential organ responsible for protein synthesis, detoxification, and bile production utilized for
indigestion. The human liver is a pinkish-brown, soft, triangular organ that usually weighs 1.44-
1.66 kg (Robinson et al., 2016). It is connected to two large blood vessels: portal vein and
hepatic artery; it is then divided into four lobes: caudate, quadrate, right and left. Each lobule
comprises millions of hepatic cells that form the basic metabolic cells of the liver. In terms of the
histology of the liver, hepatocyte entails the main tissue cell of the liver and constitutes 70 – 80
% of the liver's cytoplasmic mass. The role of hepatocytes includes the transformation of
carbohydrates, protein storage, protein synthesis, modification, excretion and detoxification of
endogenous and exogenous substances, and the synthesis of bile salts, cholesterol, and
phospholipids. Concisely, hepatocytes are the unique cells in the human body and are capable of
regeneration. There are several distinct layers of the gallbladder: the serosa, the perimuscularis,
muscularis and the mucosa. Regarding the blood flow to and from the liver, the hepatic portal
vein transport 75% of the blood to the liver. The hepatic arteries supply the remaining 25%; the
capillaries of the gastrointestinal tract are connected with the capillaries in the liver by the
5
hepatic portal system. The liver processes the nutrient-rich blood from the gastrointestinal tract
before leaving to the heart. Consequently, the liver disease involves the clogging of fats, thus
affecting liver function. According to Robinson et al. (2016), bile is composed of the following
ingredients: bile salt (10%), water (85%), fats (1%), mucus and pigments (3%), cholesterol
(0.3%), and inorganic salts (0.7%); bile can either be stored temporarily in the gallbladder or
directed into the duodenum.
In defining the pathophysiology and molecular basis of liver disease, the multiple organ
systems that malfunction includes hepatic, cerebral, cardiovascular, immunologic, renal,
pulmonary and metabolic system. In hepatic, the degree of hyperbilirubinemia forms an indicator
of liver failure severity; in cardiovascular, blood pressure and peripheral vascular resistance
decreases thus resulting in hyperdynamic circulation, increased cardiac output and heart rate; in
cerebral, there is the occurrence of portosystemic encephalopathy that is associated with
increased ammonia production in the gut; in the renal, the creatinine level indicates kidney injury
due to the low level of blood urea nitrogen (Feldman et al., 2020). Additionally, the
immunological systems exhibit deficient complement, defective opsonization, and dysfunctional
killer cells and white blood cells alongside increased bacterial translocation; in the metabolic
system, there is supervention of metabolic acidosis due to the shock developed, and there is also
hypokalemia caused by exhaustion of diuretics and decreased sympathetic tone. In the
pulmonary system, there is usually the development of noncardiogenic pulmonary edema.
To ensure proper diagnosis of liver disease, the signs and symptoms can be classified into
hepatitis symptoms, fatty liver disease symptoms, genetic condition functions, autoimmune
symptoms, cancer symptoms, liver failure symptoms and cirrhosis symptoms. For hepatitis,
common symptoms include appetite loss, fatigue, nausea, abdominal pain, jaundice and
6
vomiting. Fatty liver symptoms include severe fatigue, persistent itchiness, unexplained weight
loss and jaundice. Genetic condition symptoms include abnormal liver test results, pale and loose
stool, itchy skin, abdominal swelling, poor appetite, swelling in the legs and poor growth rate
(Newton et al., 2012). Autoimmune symptoms include fatigue, diarrhoea, nausea, jaundice and
loss of appetite. Additionally, cancer symptoms entail unintentional weight loss, vomiting,
nausea, abdominal pain, enlarged liver, fluid buildup in the abdomen and enlarged spleen. On the
other hand, cirrhosis symptoms include vomiting, nausea, discomfort, unintentional weight loss
and vomiting; eventually, the liver failure symptoms include loss of appetite, nausea, diarrhoea
and fatigue.
The laboratory features of liver disease include a range of urine and blood tests. Blood is
utilized in testing for inherited disorders or determining the quantity of oxygen in the blood.
Conversely, urine is used in checking chemicals, blood, bacteria, and cells for abnormalities or
infections. According to Lala et al. (2020), differential diagnosis of liver disease includes: acute
hepatitis that involves the portal lymph-adenopathy and thickening of gallbladder wall; the
chronic granulomatous disease that entails multiple defined abscesses; diffuse hemangioma that
involves the nearly total replacement of hepatic parenchyma by tumor; irradiated liver that
entails the chronic stage, the liver is typically contacted, fibrotic and small; liver transplantation
that involves a periportal area of low echogenicity that is often scanned after transplantation; and
chemotherapy that entails enlarged liver, echogenic in comparison to the normal renal
parenchyma (Gao et al., 2011). Finally, the complication sand prognosis of liver disease employs
predictive variables such as patient age: severe when age is below ten or above 40 years; PT:
worse when PT is prolonged; degree of encephalopathy: worse when encephalopathy is severe;
and cause of acute liver failure: better with hepatitis A or hepatitis B than with Wilson disease.
7
References
Bataller, R., & Gao, B. (2015, May). Liver fibrosis in alcoholic liver disease. In Seminars in liver
disease (Vol. 35, No. 02, pp. 146-156). Thieme Medical Publishers.
Feldman, M., Friedman, L. S., & Brandt, L. J. (Eds.). (2020). Sleisenger and Fordtran's
gastrointestinal and liver disease E-book: pathophysiology, diagnosis, management.
Elsevier.
Gao, B., Seki, E., Brenner, D. A., Friedman, S., Cohen, J. I., Nagy, L., ... & Zakhari, S. (2011).
Innate immunity in alcoholic liver disease. American Journal of Physiology-
Gastrointestinal and Liver Physiology, 300(4), G516-G525.
Gual, P., Gilgenkrantz, H., & Lotersztajn, S. (2017). Autophagy in chronic liver diseases: the
two faces of Janus. American Journal of Physiology-Cell Physiology, 312(3), C263-
C273.
Godfrey, E. L., Malik, T. H., Lai, J. C., Mindikoglu, A. L., Galván, N. T. N., Cotton, R. T., ... &
Rana, A. (2019). The decreasing predictive power of MELD in an era of changing
etiology of liver disease. American Journal of Transplantation, 19(12), 3299-3307.
Lala, V., Goyal, A., Bansal, P., & Minter, D. A. (2020). Liver function tests. StatPearls
[Internet].
Newton, J. L., & Jones, D. E. (2012). Managing systemic symptoms in chronic liver
disease. Journal of hepatology, 56, S46-S55.
8
Owen, A., & Newsome, P. N. (2015). Mesenchymal stromal cell therapy in liver disease:
opportunities and lessons to be learnt?. American Journal of Physiology-Gastrointestinal
and Liver Physiology, 309(10), G791-G800.
Rowe, I. A. (2017). Lessons from epidemiology: the burden of liver disease. Digestive
diseases, 35(4), 304-309.
Robinson, M. W., Harmon, C., & O’Farrelly, C. (2016). Liver immunology and its role in
inflammation and homeostasis. Cellular & molecular immunology, 13(3), 267-276.
