Aula 9 - Hepatic Disease Flashcards
(108 cards)
1
Q
Where is the liver located in the body?
A
It is located in the right upper quadrant of the abdomen.
2
Q
How can the liver be divided, in order to help locate pathologies?
A
Considering the vena cava, it can be separated into two lobes: right and left.
Considering the portal vein, it can be separated into four sectors: right posterior, right anterior, left medial and left lateral.
Finally, it can also be further subdivided into eight segments.
3
Q
What are the four major functions of the liver?
A
- Energy metabolism and substrate interconversion
- Protein synthesis
- Solubilization, transport and storage
- Protection and clearance
4
Q
The liver is a major intervenient in the synthesis, metabolism and interconversion of three organic compounds. Name them.
A
Carbohydrates, lipids and proteins.
5
Q
How does the liver increase glucose consumption?
A
Essentially, by two mechanisms:
* Storing glucose in the liver as glycogen (through glycogenesis);
* Promoting the synthesis of fatty acids and
cholesterol (through glycolysis to generate acetyl-CoA).
6
Q
When there is an increase of the insulin:glucagon ratio, the liver ________ (increases/decreases) insulin consumption.
A
increases
7
Q
A decrease in blood glucose levels results in a ____________ (increase/decrease) in insulin:glucagon ratio in the blood.
A
decrease
8
Q
Where are cholesterol and very-low-density lipoproteins (VLDL) stored?
A
In adipocytes (adipose tissue).
9
Q
How are fatty acids produced from glucose?
A
First, glucose is converted into acetyl-CoA (acetyl coenzyme A), through glycolysis. Then, acetyl-CoA is converted into fatty acids through the fatty acid synthesis process.
10
Q
How are fatty acids converted into triglycerides?
A
After being synthetized in the liver, fatty acids are esterified to glycerol to form triglycerides.
11
Q
What is the function of very-low-density lipoproteins (VLDL)?
A
The main function of very-low-density lipoproteins is to transport triglycerides and cholesterol to adipocytes.
12
Q
Why are triglycerides and cholesterol stored in adipocytes?
A
To serve as a source of energy for different tissues (such as muscles).
13
Q
In the liver, cholesterol can be catabolized to ________________.
A
bile acids
14
Q
How does the liver increase glucose production?
A
Essentially, by three mechanisms:
* Converting stored glygogen into glucose, through glycogenolysis.
* Converting the triglycerides stored in adipocytes into fatty acids, to be transported to the liver and synthetize ketone bodies, used for energy in the brain and muscles.
* Degrading proteins from muscles into aminoacids in order to be transported into the liver to produce glucose through gluconeogenesis.
15
Q
The production of glucose from aminoacids is called ____________ (gluconeogenesis/glycogenolysis).
A
gluconeogenesis
16
Q
What is glycogenolysis?
A
The process of conversion of glycogen stored in the liver into glucose.
17
Q
In the liver, there are three major processes occur related to lipids. Name them.
A
- Lipid acquisition
- Lipid storage
- Lipid consumption
18
Q
How can lipids be acquired by the liver through dietary fat?
A
- Dietary fats (mainly triglycerides) are digested in the small intestine, where they are emulsified by bile salts and broken down by lipases (pancreatic enzymes).
- The resulting products are absorbed by the intestine and stored in chylomicrons (lipoproteins).
- Chylomicrons enter the blood, where they are hydrolysed by lipoprotein lipase, losing triglycerides (which are taken by the tissues).
- After losing triglycerides, the chylomicron remnants (including cholesterol and fatty acids) are taken up by the liver via endocytosis.
19
Q
How can lipids (triglycerides and cholesterol) be acquired by the liver through VLDL and HDL?
A
Triglycerides and cholesterol stored in adipose tissue or found in the bloodstream can return to the liver by endocytosis of very-low-density lipoproteins (VLDL) and high-density proteins (HDL).
20
Q
How can lipids be acquired by the liver through glycolysis?
A
When there is an excess of glucose, it is converted into acetyl-CoA through glycolysis, in the liver. Then, acetyl-CoA stimulates the production of fatty acids, triglycerides and cholesterol.
21
Q
How can fatty acids be stored in the liver?
A
In the liver, fatty acids can be stored within lipid droplets or can led to the synthesis of triglycerides.
22
Q
What is the role of high-density proteins (HDL) in the lipid metabolism?
A
They collect cholesterol from the tissues and blood and return it to the liver.
Psst! That’s why it is called good cholesterol :)
23
Q
What is the main source of the body’s cholesterol?
A
Endogenous synthesis in the liver (~80% of total cholesterol), from acetyl-CoA, mainly when there is an excess of glucose.
24
Q
Which lipids predominate in chylomicron remnants?
A
Cholesterol, fatty acids and small amounts of triglycerides.
25
How are fatty acids stored in the liver?
Once in the liver, fatty acids are converted into triglycerides and stored within lipid droplets (triglyceride core with a phospholipidic monolayer containing some structural proteins around it).
26
What is lipolysis in the liver?
Lipolysis is the hydrolysis of triglycerides into glycerol and fatty acids.
27
What are the two products of lipolysis?
Glycerol and free fatty acids.
28
What is β-oxidation and where does it occur?
β-oxidation is the metabolic process by which fatty acids are oxidized to produce energy. It occurs in the mitochondria and peroxisomes.
29
What is the main purpose of β-oxidation?
Energy production.
30
How are triglycerides and cholesterol transported to other tissues?
They are packaged into very-low-density lipoproteins (VLDL) and secreted into the bloodstream.
31
How is cholesterol excreted by the liver?
Cholesterol can be transported by VLDL to other tissues or secreted into bile.
32
The liver is is known for the production and secretion of several proteins. Name some of them.
* Albumin.
* Clotting factors.
* Angiotensinogen.
* Insulin-like growth factor I.
* Apolipoproteins
* Thyroid-hormone-binding globulin
* Transferrin and ferritin
33
What is bile and what is its main function?
Bile is a "detergent-like" substance produced by the liver that facilitates the emulsification and solubilization of lipids in the aqueous environment of the intestine, aiding in lipid digestion and absorption.
34
Which types of substances are solubilized by bile that would otherwise be insoluble?
Hydrophobic substances, such as lipids.
35
What is the enterohepatic circulation of bile?
It is the recycling pathway where bile acids are secreted into the intestine, reabsorbed in the ileum, and returned to the liver via the portal circulation.
36
What is the first step of enterohepatic circulation?
Bile is synthesized by hepatocytes and transported into the biliary tract.
37
What happens to bile once it reaches the duodenum?
Bile acids promote lipid emulsification, allowing for efficient digestion and absorption of dietary fats.
38
In which part of the gastrointestinal tract are bile acids primarily reabsorbed?
The ileum.
39
How do bile acids return to the liver?
By reentering the portal blood flow.
40
How does the liver contribute to the excretion of drugs and toxic substances?
Some drugs or toxic substances (including cholesterol and bilirubin) that enter the liver via portal vein are hydrophobic, being difficult to excrete. Thus, the liver present some enzymes able to catalyze metabolic reactions that make those substances more hydrophilic, helping their solubilization and excretion.
41
Where is vitamin A stored?
Vitamin A is stored in lipid droplets that can be found in lipocytes.
42
Half of the ________ concentration found in the human body is stored in the liver.
folate
43
What is the importance of the ammonia metabolism in the liver?
The metabolism of proteins and aminoacids in the liver results in the production of ammonia which is toxic for the cells.
Thus, within the hepatocytes, ammonia is converted into urea, a much less toxic substance that is excreted by the kidneys through urine.
44
Name the 5 main hepatic biomarkers.
* Alanine transaminase (ALT) or glutamic pyruvic transaminase (GPT)
* Aspartate aminotransferase (AST) or
glutamic-oxaloacetic transaminase (GOT)
* Gamma-glutamyl transferase (γ-GT)
* Alkaline phosphatase (ALP)
* Bilirubin
45
What can elevated levels of γ-GT in the blood indicate?
High levels of γ-GT can indicate bile duct blockage or constriction, or other liver damage, since they are produced for cellular protection and detoxication.
46
How is bilirubin produced?
Bilirubin is produced by the degradation of hemoglobin, during hemolysis.
47
Bilirubin can exist in two forms. The unconjugated (or indirect) form is found in the ____________ (intestine/blood), while the conjugated (or direct) form is found in the ____________ (intestine/blood).
blood, intestine
48
Where is unconjugated bilirubin converted into conjugated bilirubin?
In hepatocytes, in the liver.
49
How can bilirubin enter the liver?
By binding to albumin in the blood.
50
What do elevated levels of bilirubin indicate?
Elevated levels of bilirubin appear in case of hepatocellular injury, hemolysis, or bile duct obstruction.
51
How is bilirubin transported from the liver into the intestine?
It is excreted in the bile.
52
Besides the main biomarkers, name other parameters that can also be used to assess liver function.
* Albumin (the liver is responsible for protein synthesis)
* Total serum protein (the liver is responsible for protein synthesis)
* Lactate dehydrogenase (LDH) (enzyme released when there is cell damage, not specific to the liver)
* Prothrombin time (PT) (the liver is responsible for coagulation factor synthesis)
53
What are the two grading systems used for liver functions?
Modified Child-Turcotte-Pugh score and Model for End-Stage Liver Disease
54
What are the three main categories of liver diseases?
* Infectious and immune disorders
* Toxic and metabolic disorders
* Structural and neoplastic disorders
55
Name some infectious and immune hepatic disorders.
* Viral hepatitis
* Autoimmune hepatitis
* Cholangitis
56
Name some toxic and metabolic hepatic disorders.
* Wilson's disease (abnormal accumulation of copper)
* Hemochromatosis (abnormal accumulation of iron)
* Alcoholic liver disease (steatosis, hepatitis, cirrhosis)
* Drug-induced (e.g., ibuprofen and paracetamol) liver injury
* Non-alcoholic fatty liver disease (fibrosis, steatosis, non-alcoholic steatohepatitis, cirrhosis)
57
Name some structural and neoplastic hepatic disorders.
* Cysts
* Cholestasis
* Hepatic benign tumors
* Hepatocellular carcinoma
* Liver cirrhosis
58
What can liver diseases cause hypoglicemia?
When the hepatocytes lose their function or there is a lost of hepatocytes, they might not be able to produce glucose from carbohydrate metabolism.
59
What can liver diseases cause hyperglicemia?
When the glucose in circulation can’t be cleared by hepatocytes, especially when there is a portal-to-systemic shunting (direct communication between the hepatic artery and the portal vein).
60
What are four possible complications of fat accumulation?
* Appearance of xanthomas (subcutaneous accumulations of cholesterol)
* Obesity
* Fatty liver disease (accumulation of fat in the liver with no signs of liver damage)
* Steatohepatitis (accumulation of fat in the
liver that already caused inflammation and
liver cell damage)
61
What is hepatic encephalopathy and what causes it?
When the normal function of the liver is compromised, the production and clearance of some essential proteins is deregulated, which affects the clearance of toxins.
Hepatic encephalopathy is a brain dysfunction due to liver dysfunction. It happens when certain toxins such as the ammonia accumulate in the blood, having a hazardous effect over the normal central nervous system function.
62
What are the two main complications of impaired bile secretion?
* Malabsorption of lipids and lipid-based vitamins (e.g., vitamins A and D), because they cannot be solubilized;
* Jaundice, which is the accumulation of bilirubin in circulation because it cannot be solubilized.
63
What are the three main types/causes of jaundice?
* Hemolytic (accumulation of bilirubin due to increased hemolysis)
* Hepatocellular (damaged hepatocytes)
* Obstructive (impaired excretion)
64
What causes hypercholesteremia?
It happens when:
* LDL can’t re-enter the liver, due to misfunction of LDL receptors, for instance);
* LDL cholesterol can not be cleared from the bloodstream, due to some impairment in the lipid metabolism.
65
What is one possible complication of hypercholesteremia?
Atherosclerosis
66
What is hepatitis?
Consists in an inflammation of the liver, which might result in liver cells death by necrosis or apoptosis.
67
What are the two main types of hepatitis?
* Infectious hepatitis
* Toxic hepatitis
68
What are the three types of infectious hepatitis?
* Viral hepatitis
* Bacterial hepatitis
* Parasitic hepatitis
69
What are the three types of toxic hepatitis?
* Alcoholic hepatitis
* Drug hepatitis
* Chemical hepatitis
70
Besides infectious and toxic hepatitis, what are the other three possible types of hepatitis?
* Radiation hepatitis
* Autoimmune hepatitis
* Genetic hepatitis
71
Name the 5 types of viral hepatitis.
* Hepatitis A
* Hepatitis B
* Hepatitis C
* Hepatitis D
* Hepatitis E
72
Which types of viral hepatitis have preventive vaccination?
Hepatitis A and Hepatitis B
73
What is the particularity of hepatitis D regarding infection?
Hepatitis D can only infect if the person has already been infected with hepatitis B.
74
T/F: Hepatitis B vaccination protects against hepatitis D.
**True.** Because Hepatitis D recquires previous infection by Hepatitis B.
75
T/F: Hepatitis is described as a chronic inflammation.
**False.** It can present both as an acute/short-term condition and as a chronic condition (> 6 months).
76
What triggers the inflammation process in viral hepatitis?
First, there is an infection with a virus that targets the liver, such as hepatitis A, B, C, D or E. The virus invades hepatocytes and damages them. The immune system is activated due to the presence of foreign particles and to the damaged tissue, starting the inflammation process.
77
Regarding incubation, refer for each of the following items which types of viral hepatitis are:
a) short-term
b) medium-term
c) long-term
a) hepatitis A and hepatitis E
b) hepatitis D
c) hepatitis B and hepatitis C
78
Name some drugs that might have toxic effects on liver cells.
* Diclofenac (voltaren)
* Acetylsalicylic acid (aspirin)
* Tamoxifen (chemotherapy drug used in breast cancer treatment)
* Methotrexate (common treatment in autoimmune disorders and some types of cancer)
* Amoxicillin-clavulanate (large spectrum antibiotic)
* Nicotinic acid
* Cocaine
79
How does alcohol intake lead to the production of NADH (coenzyme)?
The ethanol present in alcohol is converted into acetaldehyde, generating NADH. Then, acetaldehyde is converted into acetate, generating more NADH.
80
How does chronic alcohol intake lead to impaired gluconeogenesis and what are the consequences on blood glucose levels?
The ethanol present in alcohol is converted into acetaldehyde, generating NADH. Then, acetaldehyde is converted into acetate, generating more NADH.
The excess of NADH levels leads to the conversion of pyruvate into lactate (then resulting in glycolysis), instead of converting lactate into pyruvate (which then would allow glyconeogenesis).
Pyruvate + NADH ⇌ Lactate + NAD+
Since gluconeogenesis is impaired, then there is a decreased glucose production, leading to hypoglycemia.
81
How does chronic alcohol intake cause lactic acidemia?
Ethanol leads to the excess production of NADH, which causes pyruvate to te converted into lactate (instead of the other way around).
The increased lactate production in turn results in
excessive lactate delivery to the blood and a
consequent lactic acidemia.
82
How does chronic alcohol intake lead to hyperlipidemia?
Ethanol is converted into acetaldehyde, which is then converted into acetate. So, excess ethanol leads to excess acetate.
On one hand, the excess acetate is converted to acetyl-CoA, which promotes fatty acid *de novo* synthesis. ⇒ **More production of fatty acids** ⇒ **More lipids**
On the other hand, it leads to impaired fatty acid β-oxidation (which converts fatty acids into acetyl-CoA, then used for ATP production). ⇒ **Less breakdown of fatty acids** ⇒ **More lipids**
Excess fatty acids lead to an increased triglyceride and VLDL production. ⇒ **More lipids**
Therefore, the increased lipid production leads to increased lipid blood levels, causing hyperlipidemia.
83
Why does chronic alcohol intake lead to mitochondrial oxidative stress and how does it affect hepatocytes?
Excess ethanol results in excess mitochondrial NADH production, which consequently results in excess reactive oxygen species (ROS) production. This causes mitochondrial stress leading to the triggering of the mitochondrial apoptosis pathway and hepatocyte death.
84
What are the three most important general pathophysiological effects of alcohol consumption on the liver?
* Disorganizes the lipid portion of cell membranes, leading to adaptative changes in their composition;
* Alters the capacity of liver cells to cope with environmental toxins (due to altered permeability);
* Oxidation of ethanol produces acetaldehyde, a toxic and reactive intermediate.
85
Name some of the clinical manifestations of acute hepatitis.
General inflammation symptoms:
* muscle and joint pain
* fever
* feeling and being sick
* fatigue
* nausea
* loss of appetite
More specific symptoms:
* abdominal pain
* dark urine
* grey-colored stool
* itchy skin
* jaundice
86
Name the additional clinical manifestations that normally appear in chronic hepatitis (compared to acute hepatitis).
* swelled legs, ankles and feet
* blood loss in stool and vomit
* confusion/disorientation
87
Name the 4 stages of liver disease in hepatitis.
1. Acute hepatitis
2. Chronic hepatitis
3. Cirrhosis
4. Liver cancer
88
What are the three main imaging techniques used for the diagnosis of hepatitis?
* Ultrasound (evaluate liver size, texture, biliary tract, and rule out constriction/obstruction)
* Elastography (to assess the tissue stiffness and check for scarring, i.e., fibrosis)
* Computed Tomography
89
What are the main biochemical blood tests used to diagnose hepatitis?
* **Liver function tests** (ALT, AST, γ-GT, ALP, bilirubin, albumin, etc…)
* **Serological tests** (anti-HAV, anti-HBV, anti-HCV, anti-HDV, anti-HEV, etc…) - to check if it is viral hepatitis.
* **Autoimmune screenings** (ANA, IgG levels, etc…) - to check if it is autoimmune hepatitis.
* **Toxicologic and/or metabolic screenings** (drug levels, ferritin, transferrin, etc...) - to check if it is toxic hepatitis (caused by alcohol, drugs or chemicals).
90
How can biopsy help in the diagnosis of hepatitis?
It can be used in unclear cases or to assess severity and fibrosis.
91
What is cholestasis?
It's the impairment of bile secretion or flow in consequence of intrahepatic or extrahepatic
conditions.
92
What are the main clinical manifestations of cholestasis?
* Jaundice
* Dark urine and light-colored stools containing fat (steatorrhea)
* Pruritus
* Malabsorption of fat and fat soluble vitamins (e.g. D vitamin)
93
What are the main causes of intrahepatic cholestasis?
* Acute hepatitis
* Medication
* Pregnancy
* Primary biliary cholangitis
* Primary sclerosing cholangitis
94
What are the main causes of extrahepatic cholestasis?
* Obstructing gallstone
* Carcinoma of the bile duct
* Carcinoma of the head of the pancreas
* Bile duct strictures
* Primary sclerosing cholangitis
95
What are the main biochemical blood tests done to diagnose cholestasis?
* Liver function tests (ALT, AST, γ-GT, ALP, bilirubin, albumin, etc…)
* Toxicologic and/or metabolic screenings (drug levels, ferritin, transferrin,
etc...)
96
What are the expected results of biochemical blood tests in the case of cholestasis?
* Increased concentrations of serum alkaline phosphatase, γ-GT and bilirubin.
* Possibly, increased cholesterol levels (due
to poor excretion).
97
What are the main imaging techniques used to diagnose cholestasis?
* **Ultrasound** (to assess bile duct dilation or the presence of stones or masses)
* **Computed Tomography**
* **Endoscopic retrograde cholangiopancreatography** (X-ray imaging acquired after injection of a contrast agent through a endoscopy tube inserted through the mouth and into the small intestine. It is used when there’s a suspicion of a blockage in the bile ducts.)
* **Magnetic resonance cholangiopancreatography**
(specific MRI to observe bile and pancreatic ducts)
98
How can biopsy help to diagnose cholestasis?
It can be used in unclear cases or to assess intrahepatic causes.
99
What is non-alcoholic
fatty liver disease?
Fat accumulation in the liver (steatosis), which can range from absent or minimal inflammation of hepatocytes (fatty liver or steatosis) up to a condition in which there are already some liver inflammation (non-alcoholic steatohepatitis).
100
T/F: Fatty liver is a reversible condition.
True.
101
Name some of the causes of non-alcoholic fatty liver disease.
* Obesity
* High cholesterol
* High triglycerides
* Genetic predisposition
* Type 2 diabetes
* Insulin resistance
102
What happens if non-alcoholic fatty liver disease progresses? What are the next stages?
It can lead to non-alcoholic steatohepatitis, cirrhosis and, finally, hepatocellular carcinoma.
103
T/F: Non-alcoholic fatty liver disease is characterized by inflammation and steatosis.
**False.** In non-alcoholic fatty liver disease, there is no inflammation, only steatosis (presence of fat in hepatocytes).
104
Explain the development of fibrosis in the progression of non-alcoholic fatty liver disease.
The excess accummulation of fat in hepatocytes is lipotoxic and damages these cells.
In response to the liver cells damage, the liver attempts to repair itself and replace damaged cells, leading to inflammation and deposition collagen and other extracellular matrix components, formim a high density matrix.
This leads to the formation of scar tissue, especially when there are repeated or continuous
injuries, resulting in fibrosis.
105
What are the main symptoms of early-stage cirrhosis?
General inflammation symptoms, such as:
* tiredness and weakness
* nausea
* loss of appetite
* loss of weight and muscle mass
106
Is cirrhosis reversible? Why?
**No.** In cirrhosis, the normal architecture of the liver is irreversibly altered, and the scar tissue replaced normal functioning tissue, compromising the liver function.
107
What are the main symptoms of advanced cirrhosis?
* itchiness (probably due to the accumulation of toxic substances as a result of liver dysfunction)
* lower limb edema
* ascites (fluid accumulation in the abdomen)
* jaundice
* red patches on the palms and small, spider-like blood vessels on the skin (spider angiomas) above waist level
108
What are the main complications of cirrhosis?
* Hepatic encephalopathy
* Bleeding from the GI tract
* Liver cancer
