Hepatic architecture

Hepatic blood supply

Liver function
 Patient case
Patient’s chief complains:
Provided by wife: “My husband is very confused and he has been
acting strangely. This morning, he couldn’t answer my question
and seemed not to recognize me. He stopped drinking 4 year ago,
but now it seems to be getting worse”.
The patient: he is a 46 y.o., white male with a history of chronic
alcoholism.
• He was admitted to the hospital from the outpatient clinic with
abdominal swelling and confusion.
• He has unintentionally gained 15 lbs(7kg)during the past 4 weeks.
• Accordingly to his wife, the patient has not been sleeping well for
several weeks, has been feeling vary lethargic for the past 3 days.
• Before becoming confusing the patient had complained about
pain, chills, nausea, vomiting, hematemesis, loss of appetite,
light-headedness, weakness, diarrhea and dry mouth.
Medical history:
• Cirrhosis secondary to heavy alcohol was diagnosed 4 years ago with ultrasound
examination and liver biopsy (micronodular cirrhosis)
• Uncontrolled ascites and peripheral edema
• 2 episodes of upper GI hemorrhages from esophageal varices
• E.coli – induced bacterial peritonitis
• Acute pancreatitis secondary to alcohol abuse
• No history of heart and gallbladder disease
• No previous diagnosis of viral or autoimmune hepatitis.
On physical examination:
• The patient is restless, mildly jaundiced, and disoriented to time, place and
people.
• BP 110/65, Ps-83, regular (supine)
• BP 95/60, Ps -106, regular (standing)
• RR=27/min
Skin: Warm, dry and well perfused with normal turgor. Mild jaundice. Spider nevi on
chest. Palmar erythema. Several ecchymoses on lower extremities. Ginecomastia.
Abdomen: is moderately distended, firm, and slightly tender. Prominent veins
observed around umbilicus.
 Identify a minimum of 15clinical signs that are
characteristic for chronic liver failure
1. abdominal swelling 1. Weakness
2. Confusion 2. diarrhea
3. Weight gain 3. dry mouth
4. Dry and warm skin
4. Restless
5. disorientation to time, place
5. Lethargy and people
6. pain 6. Mild jaundice
7. Chills 7. Spider nevi on chest
8. Nausea 8. Palmar erythema
9. Vomiting 9. Several ecchymoses on lower
extremities
10.hematemesis
10. Ginecomastia.
11.loss of appetite 11. Prominent veins observed
12.light-headedness around umbilicus.
 What is etiology of this disease? Pathogenetic
mechanisms? (CM)
1. Alcohol is a direct hepatotoxic
2. Alcohol is indirect hepatotoxic
3. Increases intracellular
accumulation of triglycerides
4. Increases fatty acids oxidation
5. Increases lipoprotein secretion
 What is etiology of this disease? Pathogenetic
mechanisms?
1. Alcohol is a direct hepatotoxic
2. Alcohol is indirect hepatotoxic
3. Increases intracellular
accumulation of triglycerides
4. Increases fatty acids oxidation
5. Increases lipoprotein secretion
 What are the pathogenetic mechanisms? (CM)

1. Acetaldehyde – metabolic products of alcohol -

combines with proteins to form protein-
acetaldehyde adducts.
2. Aldehide – metabolic products of alcohol - combines
with proteins to form protein-aldehide adducts.
3. Alcohol activates Kupffer cells and subsequent
Stellate cells with hepatic fibrosis
4. Alcohol activates Kupffer cells and subsequent
hepatic fibrosis
5. The hepatic fibrosis is not related with Stellate cells
but with Kupffer cells
 What are the pathogenetic mechanisms?
1. Acetaldehyde – metabolic products of alcohol -
combines with proteins to form protein-
acetaldehyde adducts.
2. Aldehide – metabolic products of alcohol - combines
with proteins to form protein-aldehide adducts.
3. Alcohol activates Kupffer cells and subsequent
Stellate cells with hepatic fibrosis
4. Alcohol activates Kupffer cells and subsequent
hepatic fibrosis
5. The hepatic fibrosis is not related with Stellate cells
but with Kupffer cells
Metabolism of ethanol

MEOS

MEOS= micrososmial ethanol oxidizing system

 Alcohol abuse
The threshold for developing
alcoholic liver disease
• in men is an intake of >60–80 g/d
of alcohol for 10 years
• Women - by consuming 20–40 g/d
• Ingestion of 160 g/d - 25-fold
increased risk of developing
alcoholic cirrhosis.
• Gender-dependent differences
result from poorly understood
effects of estrogens and the
metabolism of alcohol
 Cellular pathogenesis of liver failure due to alcoholism

signal transducer and activator of transcription (STAT)

 What are changes of protein profile in the
blood and mechanisms? (CM)
1. Hypoalbuminemia due to ATP depletion in the
liver
2. Hypoalbuminemia due to ribosome's
malfunction
3. In this case is not specific paraproteinemia
4. Hypoonchia of the interstitial space
5. Hypoonchia lead to increased intravascular
fluid
 What are changes of protein profile in the
blood and mechanisms? (CM)
1. Hypoalbuminemia due to ATP depletion in the
liver
2. Hypoalbuminemia due to ribosome's
malfunction
3. In this case is not specific paraproteinemia
4. Hypoonchia of the interstitial space
5. Hypoonchia lead to increased intravascular
fluid
 What are changes of protein profile in the
blood and mechanisms? (CM)
1. It is decreased level of specific proteins:
prothrombin, fibrinogen, creatinine
2. It is decreased level of specific proteins:
prothrombin, fibrinogen, proconvertin
3. It is decreased level of clotting factors due to
lack of vitamin K
4. It is not decreased level of clotting factors,
because it is not lack of vitamin K
5. It is not characteristic hypercretinemia and
creaturia
 What are changes of protein profile in the
blood and mechanisms? (CM)
1. It is decreased level of specific proteins:
prothrombin, fibrinogen, creatinine
2. It is decreased level of specific proteins:
prothrombin, fibrinogen, proconvertin
3. It is decreased level of clotting factors due to
lack of vitamin K
4. It is not decreased level of clotting factors,
because it is not lack of vitamin K
5. It is not characteristic hypercretinemia and
creaturia
 What are changes of protein profile in the
blood and mechanisms? (CM)
1. It is reduced synthesis of urea from aminoacids
and decreased BUN
2. It is increased synthesis of urea from
aminoacids and decreased BUN
3. Hyperammoniemia with metabolic acidosis
4. Hypoammoniemia with metabolic acidosis
5. Hyperammoniemia with metabolic alkalosis
 What are changes of protein profile in the
blood and mechanisms? (CM)
1. It is reduced synthesis of urea from aminoacids
and decreased BUN
2. It is increased synthesis of urea from aminoacids
and decreased BUN
3. Hyperammoniemia with metabolic acidosis
4. Hypoammoniemia with metabolic acidosis
5. Hyperammoniemia with metabolic alkalosis
 What are changes of protein profile in the
blood and mechanisms? (CM)
1. It is reduced level of aromatic aminoacids
2. It is reduced level of branched aminoacids
3. It is increased level of aromatic aminoacids
4. It is increased level of branched aminoacids
5. Unchanged ratio of branched to aromatic
aminoacids
What are changes of protein profile in the
blood and mechanisms? (2,3)
1. It is reduced level of aromatic
aminoacids
2. It is reduced level of branched
aminoacids
3. It is increased level of aromatic
aminoacids
4. It is increased level of
branched aminoacids
5. Unchanged ratio of branched
to aromatic aminoacids
 What are the carbohydrate metabolic
changes? (CM)
1. Decreased glycogenogenesis
2. Increased glycogenogenesis
3. Glycogenolysis with glycogen depletion
4. Glycogenolysis without glycogen depletion
5. Increased gluconeogenesis
 What are the carbohydrate metabolic
changes? (CM)
1. Decreased glycogenogenesis
2. Increased glycogenogenesis
3. Glycogenolysis with glycogen depletion
4. Glycogenolysis without glycogen depletion
5. Increased gluconeogenesis
 What are the carbohydrate metabolic
changes? (CM)
1. It is characteristic of postprandial
hyperglycemia due to inability to synthesize
glycogen
2. It is characteristic of fasting hyperglycemia
due to inability to synthesize glycogen
3. It is characteristic of postprandial
hypoglycemia
4. It is characteristic of fasting hypoglycemia
5. Exaggerated fasting hyperglycemia is followed
by glucosuria
 What are the carbohydrate metabolic
changes? (CM)
1. It is characteristic of postprandial
hyperglycemia due to inability to synthesize
glycogen *
2. It is characteristic of fasting hyperglycemia
due to inability to synthesize glycogen
3. It is characteristic of postprandial
hypoglycemia
4. It is characteristic of fasting hypoglycemia *
5. Exaggerated fasting hyperglycemia is followed
by glucosuria
 What are the compensatory mechanism in
abnormal carbohydrate metabolism? (CM)
1. Excitation of SNS - transport hyperlipidemia
2. Excitation of SNS – retention hyperlipidemia
3. transport hyperlipidemia is associated with
retention hyperlipidemia
4. Decreased secretion of glucocorticoids
5. Decreased secretion of glucagon
 What are the compensatory mechanism in
abnormal carbohydrate metabolism? (CM)

1. Excitation of SNS - transport hyperlipidemia *

2. Excitation of SNS – retention hyperlipidemia
3. Transport hyperlipidemia is associated with
retention hyperlipidemia *
4. Decreased secretion of glucocorticoids
5. Decreased secretion of glucagon
 P H +
NAD

oxalacetate
 What are the carbohydrate metabolic
changes? (CM)
1. Hypoglycemia is explained by
hyperinsulinism
2. Hypoglycemia is explained by high level of
glucagon
3. Hyperaminoacidemia increases insulin level
4. Hyperaminoacidemia decreases insulin level
5. It is not characteristic lactacidemia
 What are the carbohydrate metabolic
changes? (CM)
1. Hypoglycemia is explained by hyperinsulinism *
2. Hypoglycemia is explained by high level of
glucagon
3. Hyperaminoacidemia increases insulin level *
4. Hyperaminoacidemia decreases insulin level
5. It is not characteristic lactacidemia
What are the lipid metabolic changes? (CM)

1. Decrease liposoluble vitamins A,D,E,K

2. Decrease liposoluble vitamins A,B,E,D
3. It is characteristic fatty liver due to
accumulation of triglycerides
4. It is characteristic fatty liver due to
accumulation of free fatty acids
5. It is characteristic fatty liver due to
increased beta-oxidation in liver
What are the lipid metabolic changes? (CM)

1. Decrease liposoluble vitamins A,D,E,K *

2. Decrease liposiluble vitamins A,B,E,K
3. It is characteristic fatty liver due to
accumulation of triglycerides *
4. It is characteristic fatty liver due to
accumulation of free fatty acids
5. It is characteristic fatty liver due to
increased beta-oxidation in liver
What are the mechanism of fatty liver? (CM)

1. Increase lipoprotein synthesis

2. Decreases lipoprotein synthesis
3. Increases synthesis of apoproteins in the
liver
4. Decreases synthesis of apoproteins in the
liver
5. Decreases esterification of FFA into
triglycerides
What are the mechanism of fatty liver? (CM)

1. Increase lipoprotein synthesis

2. Decreases lipoprotein synthesis *
3. Increases synthesis of apoproteins in the
liver
4. Decreases synthesis of apoproteins in the
liver *
5. Decreases esterification of FFA into
triglycerides
Fatty liver
 What biochemical tests show impairment of
liver function? (CM)
1. Decreased level of fibrinogen
2. Increased level of ALT
3. Increased level of erythropoietin
4. Hypokalemia with metabolic alkalosis
5. Hypokalemia with metabolic acidosis
 What biochemical tests show impairment of
liver function? (CM)
1. Decreased level of fibrinogen *
2. Increased level of ALT *
3. Increased level of erythropoietin
4. Hypokalemia with metabolic alkalosis *
5. Hypokalemia with metabolic acidosis
 What are hydro-electrolytic imbalance in liver
failure? (CM)
1. Hepatocyte injury – leakage of K+
2. Hepatocyte injury – leakage of Na+
3. Hepatocyte injury –influx of Na+
4. Hyponatremia is aggravated by activation of
RAAS
5. Hyperkalemia is aggravated by secondary
hyperaldosteronism
 What are hydro-electrolytic imbalance in liver
failure? (CM)
1. Hepatocyte injury – leakage of K+ *
2. Hepatocyte injury – leakage of Na+
3. Hepatocyte injury –influx of Na+ and H+*
4. Hyponatremia is aggravated by activation of
RAAS
5. Hyperkalemia is aggravated by secondary
hyperaldosteronism
What are hydro-electrolytic imbalance in liver
failure? (CM)
1. Hypocalcemia due to lack of serine that
carry blood Ca2+
2. Hypercalcemia due to retention of it
3. Hypocalcemia due to lack of colecalcipherol
4. Hypercalcemia due to excessive of
calcipherol
5. Hypercalcemia due to deficiency of
albumins that bind Ca2+
 What are hydro-electrolytic imbalance in liver
failure? (CM)
1. Hypocalcemia due to lack of serine that carry
blood Ca2+ *
2. Hypercalcemia due to retention of it
3. Hypocalcemia due to lack of colecalcipherol *
4. Hypercalcemia due to excessive of calcipherol
5. Hypercalcemia due to deficiency of albumins
that bind Ca2+
 What is the pathogeny of anemia in this
patient? (CM)
1. Depletion of ferritin storage – iron
deficiency anemia
2. Malabsorbtion of B12 and folic acid –
megaloblastic anemia
3. Anemia in this case is microcytic
4. Anemia is due to acquired haemolytic
anemia and blood loss
5. Anemia is macrocytic
 What is the pathogeny of anemia in this
patient? (CM)
1. Depletion of ferritin storage – iron deficiency
anemia *
2. Malabsorbtion of B12 and folic acid –
megaloblastic anemia
3. Anemia is microcytic *
4. Anemia is due to acquired haemolytic anemia
and blood loss
5. Anemia is macrocytic
What other changes are attested in the general
blood cell count? (CS)
1. Thrombocytosis
2. Thrombocytopenia
3. Lymphocytopenia
4. Erythrocytosis
5. Leukocytosis
What other changes are attested in the general
blood cell count? (CS)
1. Thrombocytosis
2. Thrombocytopenia *
3. Lymphocytopenia
4. Erythrocytosis
5. Leukocytosis
 What are the coetaneous changes and
mechanisms? (CM)
1. Palmar eryrhema due to decreased blood
pressure
2. Jaundice due to increased unconjugated
bilirubin level
3. Jaundice du to increased unconjugated and
conjugated bilirubin level
4. Palmar erythema due to increased blood flow
5. Spider nevi that are seen in the lower part of
the body
 What are the coetaneous changes and
mechanisms? (CM)
1. Palmar eryrhema due to
decreased blood pressure
2. Jaundice due to increased
unconjugated bilirubin level
3. Jaundice du to increased
unconjugated and conjugated
bilirubin level *
4. Palmar erythema due to
increased blood flow *
5. Spider nevi that are seen in the
lower part of the body
 What is the pathophysiology of portal
hypertension? (CM)
1. Alcohol disturbs liver architectonics – increases
the resistance in portal vein
2. Alcohol disturbs liver architectonics – increases
the resistance in portal artery
3. Locally is decreased production of NO
4. Locally is decreased production of ET-1
5. Locally is decreased production of Ang-2
 What is the pathophysiology of portal
hypertension? (CM)
1. Alcohol disturbs liver architectonics – increases
the resistance in portal vein *
2. Alcohol disturbs liver architectonics – increases
the resistance in portal artery
3. Locally is decreased production of NO *
4. Locally is decreased production of ET-1
5. Locally is decreased production of Ang-2
 What is the pathophysiology of portal
hypertension? (CM)
1. Increased portal pressure due to hyperdynamic
circulation
2. Increased portal pressure due to arterial
vasodilation caused by NO
3. Increased portal pressure due to arterial
vasoconstriction caused by Ang- 2
4. Increased portal pressure due to arterial
vasoconstriction caused by ET-1
5. Splanchnic vasoconstriction is caused by PGI2
 What is the pathophysiology of portal
hypertension? (CM)
1. Increased portal pressure due to hyperdynamic
circulation *
2. Increased portal pressure due to arterial
vasodilation caused by NO
3. Increased portal pressure due to arterial
vasoconstriction caused by Ang- 2*
4. Increased portal pressure due to arterial
vasoconstriction caused by ET-1 *
5. Splanchnic vasoconstriction is caused by PGI2
Liver fibrosis
 Normal Portal vein Portal hypertension =
pressure = 4-8 mmHg above 12mmHg
Causes of portal hypertension
Portal hypertension
Consequences of portal hypertension
Consequences of portal hypertension
 What are the pathogenetic mechanisms of
ascites in this patient? (CM)
1. Overfill theory – initial hypovolemia and after that
activation of RAAS
2. Overfill theory – initial activation of RAAS due to lack
of aldosteron breakdown
3. Underfill theory– initial activation of RAAS due to
lack of aldosteron breakdown
4. Underfill theory – initial hypovolemia and after that
activation of RAAS
5. Underfill theory– initial activation of lymphatic
drainage
 What are the pathogenetic mechanisms of
ascites in this patient? (CM)
1. Overfill theory – initial hypovolemia and after
that activation of RAAS
2. Overfill theory – initial activation of RAAS due to
lack of aldosteron breakdown *
3. Underfill theory– initial activation of RAAS due to
lack of aldosteron breakdown
4. Underfill theory – initial hypovolemia and after
that activation of RAAS *
5. Underfill theory– initial activation of lymphatic
drainage
 What are the pathogenetic mechanisms of
ascites in this patient? (CM)
1. Hypoonchia and decrease reabsorbtion of
plasma
2. Increases peripheral vasodilators with increased
filtration
3. Increased lymphogenesis and reabsorbtion of
fluid from the peritoneal space
4. Increases peripheral vasoconstrictors with
increased filtration
5. Hypoonchia and increase reabsorbtion of
plasma
 What are the pathogenetic mechanisms of
ascites in this patient? (CM)
1. Hypoonchia and decrease reabsorbtion of
plasma from the peritoneal space *
2. Increases peripheral vasodilators with increased
filtration *
3. Increased lymphogenesis and reabsorbtion of
fluid from the peritoneal space
4. Increases peripheral vasoconstrictors with
increased filtration
5. Hypoonchia and increase reabsorbtion of
plasma from the peritoneal space
 NO production

!
Mechanism of ascites
 What is the mechanism of encephalopathy ?
(CM)
1. Toxic substances from the portal blood pass
blood-brain barrier
2. NH4 pass blood brain barrier
3. At the level of atrocyties - glutamic acid is
converted to glutamine
4. Decreased consumption of alpha-ketoglutaric
acid with impairment of Krebs cycle
5. NH3 pass blood brain barrier
 What is the mechanism of encephalopathy ?
(CM)
1. Toxic substances from the portal blood pass
blood-brain barrier *
2. NH4 pass blood brain barrier
3. At the level of atrocyties - glutamic acid is
converted to glutamine
4. Decreased consumption of alpha-ketoglutaric
acid with impairment of Krebs cycle
5. NH3 pass blood brain barrier *