Pathophysiology Report: Liver Cirrhosis Leading to HPS and HRS

This report delves into the pathophysiology of liver failure, focusing on how cirrhosis leads to hepatopulmonary syndrome (HPS) and hepatorenal syndrome (HRS). It explains the problems associated with a cirrhotic liver, including blood flow disturbances due to fibrosis and scar tissue formation. The report elucidates hepatic portal hypertension (HPH), its link to cirrhosis, and the compensatory mechanisms of the splanchnic circulation. Furthermore, it details the characteristics and causes of HPS, emphasizing ventilation/perfusion (V/Q) mismatch and dyspnea. Finally, the report discusses hepatorenal syndrome (HRS), explaining why the kidneys receive insufficient blood for filtration due to HPH and HPS, and identifies the kidney hormone system implicated in HRS development, contrasting its normal function with its role in HRS. The report concludes that liver cirrhosis leads to the development of hepatic portal hypertension (HPH) that consequently results in the development of hepatopulmonary syndrome (HPS) hence the patient with cirrhotic liver experiences shortness of breath and kidney problems.

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PATHOPHYSIOLOGY - LIVER FAILURE
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PATHOPHYSIOLOGY - LIVER FAILURE
Q1. Describe what the problem is with a cirrhotic liver and why it causes blood flow problems
Liver cirrhosis is caused by various chronic liver conditions that progress to liver fibrosis.
Research shows that there are various factors that contribute to a cirrhotic liver which include:
alcoholism, fatty liver diseases and chronic hepatitis C virus infection. There are several cells
that are involved in liver cirrhosis as well as cytokines and miRNAs that are involved in the
initiation and progression of liver cirrhosis. Capillarization and defenestration of the liver
sinusoidal cells is the most significant factor that causes hepatic dysfunction in liver cirrhosis
(Pinzani, Rosselli & Zuckermann, 2011 p.281). The activated Kupffer cells are the major
contributor of the destruction that occurs to the hepatocytes which lead to the activation of the
hepatic stellate cells (HSCs). Consequently, there is repeated and continuous cycles of apoptosis
and regeneration of the hepatocytes which leads to the progression of the pathogenesis of the
liver cirrhosis (Tsochatzis, Bosch & Burroughs, 2014 p.1760). At the molecular level, it has been
found out that numerous cytokines are involved in the mediation of the signalling pathway which
is involved in the regulation of the activation of HSCs and fibrinogenesis hence leading to the
development of a cirrhotic liver. The fibrosis and scar tissue formation limits the blow flow in a
cirrhotic liver hence leading to blood flow problems. Therefore, blood capillaries are visible on
the skin on the region around the upper abdomen. Due to limited blood flow into the liver the
patient experiences jaundice, swelling of the abdomen, fatigue, insomnia, weakness, nausea, loss
of appetite and itchy skin. Portal hypertension due to liver cirrhosis causes oesophagal varices
and when the blood vessels enlarge they rapture hence contributing to the blood flow problems
(García-Pagán, Gracia-Sancho, Bosch, 2012 p. 458). Portal hypertension can also result in

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shunting of the portal venous system through the periumbilical veins leading to caput medusa (a
pattern that resembles the head of Medusa).
Q2. What is hepatic portal hypertension (HPH) and why is it linked to cirrhosis?
Hepatic portal hypertension (HPH) refers to the increased pressures experienced in the
portal venous system which is a prominent vein that that leads to the liver (Dietrich, Serra &
Jedrzejczyk, 2010 p. 4). Portal hypertension is usually caused by liver diseases such as liver
cirrhosis that leads to obstruction as well as other structural changes that result in increased flow
in the portal circulation and also increased hepatic resistance. Gastrointestinal haemorrhage is the
main initial symptom that presents in patients with hepatic portal hypertension. The most
significant cause of hepatic portal hypertension (HPH) is liver cirrhosis (Parisi et al. 2013 EP1).
Cirrhosis forms a scar and the scar tissue blocks the free blood flow via the parenchyma of the
liver hence causing elevated blood pressure throughout the portal vein. Normally, the vascular
channels in the liver are smooth, however, cirrhotic liver causes them to be irregular and tortuous
hence leading to an increase in the resistance to flow resulting into hepatic portal hypertension.
The patients with more advanced cirrhotic liver leading to hepatic portal hypertension present
with additional symptoms such as jaundice, angioma, ascites, coagulopathy, caput Medusa and
hepatic encephalopathy (Bosch, Abraldes, Fernández & García-Pagán, 2010 p.558).
Splenomegaly, as well as dilated wall veins of the abdomen, are often seen in individuals with
hepatic portal hypertension.
Q3. What will the blood vessels of the splanchnic circulation do to try to overcome hepatic
portal hypertension

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The splanchnic circulation includes the blood circulation to the gastric, hepatic, splenic
circulations, colon, small intestines and pancreas. The artery that supplies the blood to the
splanchnic region is comprised of the abdominal aorta, inferior and superior mesenteric arteries,
and the coeliac artery. Under the normal physiological conditions, the blood flow in the
splanchnic circulation is normally controlled through the intrinsic and extrinsic mechanisms. The
intrinsic involves both metabolic and myogenic mechanisms while extrinsic includes the
humoral and autonomic mechanisms (Thomas, 2011 p.30). Disorders of the splanchnic
circulation that may result from hepatic portal hypertension leads to multi-organ dysfunction
syndrome. In patients with portal hypertension due to liver cirrhosis, the rise in the splanchnic
flow of blood is due to the vasodilation of the arterial splanchnic vessels. Therefore, the rise in
the splanchnic blood flow makes portal hypertension worse. The increase in the splanchnic blood
flow is caused by the vasodilatation of the arterial splanchnic blood vessels as well as the
opening of the collateral circulation. In portal hypertension, a number of vasoactive systems and
substances such as nitric oxide, carbon monoxide, cyclooxygenase derivatives and endogenous
cannabinoids are activated hence leading to the increased splanchnic vasodilatation so as to
overcome hepatic portal hypertension (Iwakiri & Groszmann, 2014 p.3).
Q4. The issues in questions 1-3 above can lead to hepatopulmonary syndrome (HPS). What is
HPS, what is it characterized by and what specifically is causing it?
Hepatopulmonary syndrome (HPS) is an abnormality that occurs in the lungs of an
individual which is caused by the diseases. The disease causes shortness of breath due to low
oxygen levels. This condition results since the liver are not working properly hence the
capillaries in the lung become dilated or enlarged. In the normal state, the capillaries in the lungs
carry the RBCs into the lungs such that oxygen flows into the alveoli hence oxygen is distributed

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to other parts of the body (Machicao & Fallon, 2014 Ep.1). However, when the capillaries in the
lungs are dilated, the RBCs are unable to absorb oxygen properly hence the shortness of breath
due to low levels of oxygen. There are various signs and symptoms that are associated with
hepatopulmonary syndrome as it causes low oxygen levels in the blood. Due to low levels of
oxygen the patient experiences shortness of breath whose severity progresses with time. Since
there are low levels of oxygen travelling via the body, the fingertips become blue and
occasionally the fingernails change shape resulting into clubbing. The patient also experiences
breathlessness in the standing or sitting position but feels better when left lying flat. The specific
cause of hepatopulmonary syndrome has been determined as the increased liver production as
well as reduced liver clearance of vasodilators which involves nitric oxide. The dilation of the
blood capillaries leads to overperfusion that is relative to ventilation hence resulting into
hypoxemia and ventilation-perfusion mismatch. Cirrhotic liver results into high output failure
leading to less time in the capillaries per RBCs which exacerbates hypoxemia (Grace & Angus,
2013 p.213).
Q5. Why does the change in lung blood flow in HPS cause V/Q mismatch? What is dyspnea and
why does it occur once V/Q mismatch develops?
Ventilation/perfusion (V/Q) is a ratio that is used in respiratory physiology to assess the
effectiveness and also adequacy of the matching of two key variables: ventilation (the air that
reaches the lung alveoli) and perfusion (the blood that reaches the lung alveoli through the
capillaries (Jobse et al. 2014 p.42). The changes in the lung flow of blood in patients with
hepatopulmonary syndrome (HPS) causes V/Q mismatch due to vasodilatation and the
development of a shunt. The blood flows into the lungs is not usually uniform hence it leads to
ventilation-perfusion mismatch which restricts oxygen molecules from reaching the capillary

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centre and haemoglobin in the RBCs. Dyspnea also referred to as shortness of breath is the
feeling that an individual cannot breathe well enough. This is the experience of breathing
discomfort and its burden has an adverse effect on the activities of daily living. The sensations
experienced during dyspnea include chest tightness, effort while breathing in a resting place, air
hunger whereby the patient feels that there is not enough oxygen. Dyspnea occurs when V/Q
mismatch develops since due to vasodilation the patient has less oxygen reaching the brain and
other body parts hence leading to shortness of breath (Singh, 2016 p.78).
Q6. A further complication of these processes is hepatorenal syndrome (HRS) because the
kidney can’t receive enough blood (this is called underfill). Why aren’t the kidneys receiving
enough blood for filtration once HPH and HPS occur?
Hepatorenal syndrome (HRS) is a complication of liver cirrhosis whereby the liver does
not receive enough blood for filtration as soon as HPS and HPH. The deteriorating functions of
the liver cause fatal changes in the circulation that supplies the human intestines hence altering
the vessel tone as well as blood flow in the kidneys hence there is not enough blood for filtration.
It has been confirmed that the kidney failure of hepatorenal syndrome is due to these changes in
the blood flow and not the direct damage to the kidney. Therefore, the main theory which is
referred to as the Underfill Theory whereby due to the constriction of blood vessels in the kidney
circulation as a result of dilation of splanchnic circulation blood vessels, there is the activation of
the renin-angiotensin system and renin secretion. These two consequences lead to
vasoconstriction of blood vessels in the kidney hence less blood is available for filtration
(European Association For The Study Of The Liver, 2010 p.400).
Q7. What is the kidney hormone system implicated in the development of HRS and how does it

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normally work, in comparison to what it is causing in HRS development?
In patients with the Hepatorenal syndrome (HRS), the kidney hormone system is
implicated in its development and the complications that accompany it. The most notable event
is the activation of the renin-angiotensin system as well as renin secretion. Normally, renin is
part of the RAAS (Renin-Angiotensin-Aldosterone System). When there is insufficient blood
flow to the kidneys, renal juxtaglomerular apparatus cells start synthesizing renin which is a
protein enzyme that catalyzes the conversion of angiotensin to angiotensin I that is finally
converted into angiotensin II. Angiotensin II stimulates the synthesis of aldosterone and also
causes vasoconstriction (de Kloet, Krause & Woods, 2010 p.525). However, in Hepatorenal
syndrome (HRS), there is excessive activation of renin-angiotensin system as well as increased
amount of resin that is secreted which leads to marked vasoconstriction of the blood vessels in
the kidney resulting to reduced amounts of blood available for filtration (Siragy & Carey, 2010
p.545).
Final Synthesis Of The Material
Introduction
Liver cirrhosis leads to the development of hepatic portal hypertension (HPH) that
consequently results in the development of hepatopulmonary syndrome (HPS) hence the patient
with cirrhotic liver experiences shortness of breath. All these problems are due to the disruption
of the structure of the liver blood vessels that causes portal hypertension hence causing kidney
problems.
Body

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Liver cirrhosis leads to the formation of scars which affects the structural and functional
aspects of the liver. This leads to circulation problems as the capillaries become fenestrated and
destroyed. The impaired blood circulation leads to hepatic portal hypertension (HPH) since the
vascular channels in the liver become irregular and tortuous hence leading to an increase in the
resistance to flow. Therefore, the following signs and symptoms are experienced: as jaundice,
angioma, ascites, coagulopathy, caput Medusa, splenomegaly, dilation of the veins that are found
on the wall of the abdomen and hepatic encephalopathy. Disorders of the splanchnic circulation
that may result from hepatic portal hypertension leads to multi-organ dysfunction syndrome.
Consequently, liver cirrhosis and hepatic portal hypertension (HPH) leads to the development of
hepatopulmonary syndrome (HPS) whereby an individual experiences shortness of breath due to
the dilation of the blood capillaries which causes overperfusion that is relative to ventilation
hence resulting into hypoxemia and ventilation-perfusion mismatch due to vasodilatation and the
development of a shunt. Research shows that hepatopulmonary syndrome (HPS) is worsened by
excessive activation of the renin-angiotensin system and increased renin secretion.
Conclusion
It can be concluded that the formation of scar tissue due to liver cirrhosis causes of
hepatic portal hypertension (HPH) as well as the hepatopulmonary syndrome (HPS). This is
because liver cirrhosis results in functional and structural abnormalities that affect the liver
vascular system. Consequently, this causes hepatic portal hypertension and problems in the
splanchnic circulation both of which results in hepatopulmonary syndrome. Liver cirrhosis
complications also affect the functions of the kidney as it leads to excessive activation of the
RAAS which increases renin secretion.

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References
Bosch, J., Abraldes, J.G., Fernández, M. and García-Pagán, J.C., 2010. Hepatic endothelial
dysfunction and abnormal angiogenesis: new targets in the treatment of portal
hypertension. Journal of hepatology, 53(3), pp.558-567.
de Kloet, A.D., Krause, E.G. and Woods, S.C., 2010. The renin angiotensin system and the
metabolic syndrome. Physiology & behavior, 100(5), pp.525-534.
Dietrich, C.F., Serra, C. and Jedrzejczyk, M., 2010. Ultrasound of the liver. Bad Mergentheim.
European Association For The Study Of The Liver, 2010. EASL clinical practice guidelines on
the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in
cirrhosis. Journal of Hepatology, 53(3), pp.397-417.
García-Pagán, J.C., Gracia-Sancho, J. and Bosch, J., 2012. Functional aspects on the
pathophysiology of portal hypertension in cirrhosis. Journal of hepatology, 57(2), pp.458-461.
Grace, J.A. and Angus, P.W., 2013. Hepatopulmonary syndrome: update on recent advances in
pathophysiology, investigation, and treatment. Journal of gastroenterology and
hepatology, 28(2), pp.213-219.
Iwakiri, Y. and Groszmann, R.J., 2014. Pathophysiology of portal hypertension. In Variceal
Hemorrhage (pp. 3-14). Springer, New York, NY.
Jobse, B.N., McCurry, C.A., Morissette, M.C., Rhem, R.G., Stämpfli, M.R. and Labiris, N.R.,
2014. Impact of inflammation, emphysema, and smoking cessation on V/Q in mouse models of
lung obstruction. Respiratory research, 15(1), p.42.

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Machicao, V.I. and Fallon, M.B., 2014. Hepatopulmonary syndrome. Semin Respir Crit Care
Med, 33(1).
Parisi, G.F., Di Dio, G., Franzonello, C., Gennaro, A., Rotolo, N., Lionetti, E. and Leonardi, S.,
2013. Liver disease in cystic fibrosis: an update. Hepatitis monthly, 13(8).
Pinzani, M., Rosselli, M. and Zuckermann, M., 2011. Liver cirrhosis. Best practice & research
Clinical gastroenterology, 25(2), pp.281-290.
Singh, V., 2016. Acute respiratory distress syndrome. J Lung Pulm Respir Res, 3(2), p.00078.
Siragy, H.M. and Carey, R.M., 2010. Role of the intrarenal renin-angiotensin-aldosterone system
in chronic kidney disease. American journal of nephrology, 31(6), pp.541-550.
Thomas, G.D., 2011. Neural control of the circulation. Advances in physiology education, 35(1),
pp.28-32.
Tsochatzis, E.A., Bosch, J. and Burroughs, A.K., 2014. Liver cirrhosis. The Lancet, 383(9930),
pp.1749-1761.