Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Path II Block III > Liver Pathology > Flashcards

Liver Pathology Flashcards

1
Q

What is the blood supply of the liver like?

A

Dual blood supply: portal vein (60-70%, brings blood form intestines) and hepatic artery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the anatomic unit of liver called?

A

Classic liver lobule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the functional unit of liver called?

A

Acinus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What does the portal triad contain?

A

Branch of hepatic artery, branch of portal vein, and bile ductule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe the flow of blood and bile in liver?

A

Blood flows from portal tract via the sinusoids towards the central vein
Bile flows from central vein to the portal triad
BLOOD AND BILE NEVER MIX IN THE LIVER!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How is the acinus divided?

A

3 zones
Zone 1 –> periportal zone –> hepatocytes located around the portal triad (receive the most oxygen and nutrients); damaged in yellow phosphorus poisoning and pre-eclampsia
Zone 2 –> mid-zone –> affected in yellow fever
Zone 3 –> centrilobular zone –> hepatocytes located around the central vein (receives the least amount of oxygen and nutrients); involved in fatty change, tissue hypoxia, acetaminophen poisoning

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the clinical manifestations of liver diseases?

A

Generalized pruritis (deposition of bile salts in skin)
Right upper quadrant pain (hepatomegaly with swelling of capsule or gall bladder swelling)
Dark colored urine (bilirubinuria with or without urobilinogen)
Light colored stool (obstruction of bile ducts)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the clinical manifestations of complications of liver diseases?

A

Alteration in mental status and sleep pattern –> early stages of hepatic encephalopathy
Swelling of abdomen and legs –> ascites due to portal hypertension or increased capillary oncotic pressure
Impotence in males –> hyperesterinism secondary to alcoholic cirrhosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is AST (aspartate transaminase) and when is it elevated?

A

AST is a mitochondrial enzyme in hepatocytes. It is also found in muscle, hearts, and RBCs. It is elevated when there is damage to mitochondria of cells such as in alcoholic hepatitis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why is AST elevated in alcoholic hepatitis and ALT elevated in viral hepatitis?

A

AST is elevated in alcoholic hepatitis because alcohol is a mitochondria enzyme so when there is alcoholic hepatitis, mitochondria are destroyed in hepatocytes and since AST is a mitochondrial enzyme, it is more elevated than ALT.
ALT is elevated in viral hepatitis because virus lead to damage and necrosis of the hepatocytes and that results in leakage of cytosolic enzymes such as ALT.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is ALT (alanine transaminase) and when is it elevated?

A

ALT is a cytosolic enzyme only present in the liver, and no other cells. It is elevated when there is damage to hepatocytes such as in the case of viral hepatitis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is ALP (alkaline phosphatase) and when is it elevated?

A

ALP is present in many tissues such as liver, bone and placenta. It is elevated when there is obstruction to an organ. If it is elevated in conjunction with GGT, then there is obstruction to the flow of bile.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is GGT (gamma glutamyltransferase) and when is it elevated?

A

GGT is primarily located in the smooth muscle of the liver. There is increased synthesis of GGT when there is obstruction to the flow of bile in the liver or when there is administration of drugs that enhance cytochrome P450 system (eg, alcohol, phenobarbital).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why is PT (prothrombin time) elevated in liver disease?

A

PT is a marker of hepatic protein synthesis. Liver is responsible for synthesizing proteins such as albumin and also coagulation factors. PT in increased in impaired hepatocellular function because PT checks the integrity of the extrinsic pathway of coagulation which is consisted of factor VII which is produced by the liver and since factor VII has the shortest half life, it is eliminated first in hepatic disease and hence PT is increased.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the different tumor markers for liver disease?

A

CEA (carcinoembryonic antigen) –> marker of metastatic disease to liver.
AFP (alpha fetoprotein) and AAT (alpha 1 antitrypsin) –> increased in hepatocellular carcinoma in adults and hepatoblastoma in children.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is jaundice?

A

It is yellowish discoloration of mucous membranes, first noticed in the sclera of the eye. It presents when there is bilirubin level of >2.5.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the normal serum bilirubin?

A

Normal serum bilirubin is </= 1.2.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why does the liver form bile?

A

To eliminate bilirubin and excess cholesterol. Bile salts help in emulsification of fat in gut.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is cholestasis?

A

It refers to system retention of not only bilirubin, but also other solutes normally eliminated in bile (especially bile salts and cholesterol).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the normal pathway for bilirubin metabolism.

A

Senescent (old) red blood cells (RBCs) are phagocytosed by splenic macrophages.
Protoporphyrin (from heme) is converted into unconjugated bilirubin (UCB= indirect bilirubin).
UCB is lipid-soluble (not water soluble).
Albumin carries UCB to the liver.
Uridine glucuronide transferase (UGT) in hepatocytes conjugates bilirubin.
Conjugated bilirubin (CB= direct bilirubin) is transferred to bile canaliculi to form bile.
CB is water soluble.
Bile is stored in the gall bladder.
Bile is released into the small bowel via CBD (common bile duct) to aid in digestion.
Intestinal bacteria convert CB to urobilinogen (UBG).
UBG is spontaneously oxidized to urobilin.
Urobilin produces the brown color of stool.
Urobilinogen is also partially reabsorbed into the blood and filtered by kidney, making the urine yellow.
UCB and CB is never a normal finding in the urine.
CB does not come in contact with blood, so most of the bilirubin in blood is UCB (about 80%).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the common causes of jaundice?

A

Increased production of UCB.
Decreased hepatic uptake or conjugation of UCB.
Obstruction to the flow of bilirubin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How is jaundice classified?

A

CB impaired production of UCB or decreased hepatic uptake or conjugation of UCB
CB 20-50% –> viral or alcoholic hepatitis
CB >50% –> obstruction to the flow of bile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the cause of impaired production of UCB?

A

Extravascular hemolytic anemias –> hereditary spherocytosis, sickle cell disease, Rh and ABO incompatibility, hemolytic disease of the newborn and warm AIHA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the mechanism of bilirubin metabolism in impaired production of UCB?

A

Spherical RBCs are degraded by macrophages in the spleen.
This leads to increased macrophage production of UCB.
This causes an increase in serum UCB (++; CB% <20%).
There is also corresponding increase in uptake and conjugation of UCB, conjugation to CB (++), and conversion of CB in the bowel to UBG (++).
Increase in UBG causes darkening of the stool.
There is a greater percentage of UBG recycled back to the liver and urine.
The increase in urine UBG (++), darkens the color of urine.
Because RBCs contain the enzyme aspartate aminotransferase (AST), hemolysis of RBCs causes an increase in serum AST.
Alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) levels are normal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the causes of decreased conjugation of UCB?

A

Physiologic jaundice of the newborn
Crigler-Najjar syndrome type I and II
Gilbert’s syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Describe physiological jaundice of the newborn.

A

Commonly noted at birth and peaks on 3rd day.
Characterized by mild unconjugated hyperbilirubinemia.
Immature hepatic machinery for conjugating (relative deficiency of UDP-glucuronyl transferase) –> increased UCB –> jaundice.
UCB is lipid soluble and can deposit in the basal ganglia (kernicterus) leading to neurological deficits and death.
Treatment is phototherapy (makes UCB water soluble).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Describe Crigler-Najjar syndrome type I and II.

A 
It is a familial disorder characterized by unconjugated hyperbilirubinemia due to decreased or absent glucuronyl transferase enzyme (conjugates UCB to CB). 
Type I (severe form) --> complete absence of enzyme; presents early in life and patients die within a few years (due to damage to CNS --> kernicterus); clinical findings include jaundice and kernicterus; treatment involves liver transplantation. 
Type II (mild form) --> less severe due to decreased production of the enzyme; responds to phenobarbital therapy which increases liver enzyme synthesis (decreasing the level of UCB),
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the cause for decreased hepatic uptake of UCB?

A

Gilbert’s syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Describe Gilbert’s syndrome.

A

Occurs in almost 7% of the population.
Characterized by modest increase in serum unconjugated bilirubin.
Cause:
Mild decrease in glucuronyl transferase activity leading to defective conjugation of bilirubin.
Some patients have decreased hepatobiliary uptake.
Signs and symptoms:
Presents in teens- 20s, often an incidental finding.
Only manifestation is intermittent jaundice with increased serum unconjugated bilirubin.
Jaundice exacerbated by fasting or increase in alcohol intake, or stress (e.g. infection).
Diagnosis:
24-hr fast causes doubling of bilirubin.
Liver is normal, liver biopsy not necessary.
No clinical consequences ; no treatment required.

30
Q

What is the mechanism of bilirubin metabolism in viral and alcoholic hepatitis?

A

Serum UCB is increased due to a decrease in uptake and conjugation.
Serum and urine CB are increased because of liver cell necrosis and disruption of bile ductules between hepatocytes.
Urine UBG is increased because UBG is redirected from the liver to the kidneys.
Because there is an increase in serum UCB and CB, there is mixed hyperbilirubinemia with CB 20-50%.
In viral hepatitis, ALT is higher than AST and there is slight increase in ALP and GGT.
In alcoholic hepatitis, AST is higher than ALT because alcohol is a mitochondrial poison and there is increased levels of GGT.

31
Q

What are the causes of decreased intrahepatic bile flow?

A

Dubin Johnson syndrome
Rotor’s syndrome
Drug induced (oral contraceptives)
Primary biliary cirrhosis (PBC)

32
Q

Describe Dubin Johnson syndrome.

A

Autosomal recessive condition characterized by conjugated hyperbilirubinemia due to defective conjugated bilirubin transport and excretions which leads to impaired secretion of bile into intrahepatic bile duct.
Clinically manifests as brown to black discoloration in the liver because of deposition of granules of very dark pigment (polymerized epinephrine metabolites).
There is also hepatomegaly present.

33
Q

How is Rotor’s syndrome different from Dubin Johnson syndrome?

A

In Rotor’s syndrome, do not see the black (abnormal) pigment.

34
Q

What are causes for decreased extraheptic bile flow?

A

Gall stone in common bile duct

Carcinoma of the head of pancreas

35
Q

What is the mechanism of bilirubin metabolism in obstructive jaundice?

A

There is an increase in serum and urine CB due to obstruction of intrahepatic or extrahepatic bile flow.
This causes increased pressure in the intraheptic bile ductules leading to rupture and egress of CB into sinusoidal blood.
There is absence of UBG in the stool (light-colored) and urine.
CB >50% and there is marked increase in serum ALP and GGT and only a slight increase in serum AST and ALT.

36
Q

What are the two ways in which the liver responds to cirrhosis?

A

Hepatocytes proliferating to form regenerating nodules.

ito cells getting converted to myofibroblasts forming whitish, fibrous bands between the regenerating nodules.

37
Q

What are the three main characteristics of cirrhosis?

A

Bridging fibrous septae –> linking portal tracts to each other and to central veins.
Regenerating parenchymal nodules of encircled hepatocytes.
Disruption of architecture of entire liver.

38
Q

Is the fibrosis in cirrhosis reversible?

A

No.

39
Q

How is diagnosis of cirrhosis made?

A

Needs to have all three characteristic features.

40
Q

Describe the regenerating nodules in cirrhosis.

A

Develop as a result of hepatocyte reaction to injury.
They lack normal liver architecture.
They are surrounded by bands of fibrosis.
The compress sinusoids and central veins –> intrasinusoidal hypertension due to reduction in number of functional sinusoids, and increase in hydrostatic pressure in portal vein.

41
Q

What is the pathogenesis of cirrhosis?

A

Ito cells (stellate cells), under the influence of TGF-B, transform into myofibroblast like cells.
These myofibroblast like cells produce collagen type I and III (fibrous tissue) –> synthesis is stimulated by chronic inflammatory condition with cytokine generation.
Collagen is deposited in all parts of the liver lobule.
Fibrosis of the liver in cirrhosis is irreversible.
Sinusoidal endothelial cells lose fenestrations.

42
Q

What are the clinical manifestations of cirrhosis?

A

It may be clinically silent, but ultimately leads to anorexia, weight loss, weakness, wasted extremities, and jaundice.

43
Q

Why is there jaundice present in cirrhosis?

A

Jaundice develops because the normal liver cells are not present to conjugate the unconjugated bilirubin.
This leads to formation of regenerating nodules of hepatocytes which compress upon the sinusoids leading to portal hypertension.
The nodules also compress on the normal bile ductules and bile is not able to flow out of the liver imparting the greenish color to the liver.
The bilirubinemia is mixed (both UCB and CB).

44
Q

What the ultimate causes of death in cirrhosis?

A

Hepatic failure
Complications of portal hypertension
Hepatocellular carcinoma

45
Q

What are the complications of cirrhosis?

A 
Hepatic failure 
Portal hypertension 
Ascites
Heptorenal syndrome 
Hyper-esterinism in males
Hepatocellular carcinoma
46
Q

When does hepatic failure develop?

A

When >80-90% of liver function is lost.

47
Q

What are the clinical manifestations of hepatic failure?

A

Multiple coagulation defects due to inability to synthesize coagulation factors –> increase in PT and APTT –> produces a hemorrhagic diathesis.
Hypoalbuminemia from decreased synthesis of albumin –> dependent pitting edema and ascites
Hypocalcemia because there is no albumin to bind to the calcium.

48
Q

How is hepatic failure classified?

A

Chronic hepatocyte damage –> main cause is cirrhosis

Acute hepatocyte damage –> fulminant hepatic failure

49
Q

What is hepatic encephalopathy?

A

Life threatening reversible metabolic disorder of CNS and neuromuscular transmission.

50
Q

What is the etiopathogenesis of hepatic encephalopathy?

A

Increase in serum ammonia.

Increase in aromatic amino acids –> converted to false neurotransmitters.

51
Q

How does ammonia affect the CNS?

A 
Alteration in sleep pattern. 
Tendency to sleep more. 
Changes in mental status. 
Development of coma. 
Death.
52
Q

What are the factors that can precipitate encephalopathy?

A

Increased protein.
Alkalosis –> keeps ammonia in NH3 state.
Diuretics –> produces metabolic alkalosis.
Sedatives.
Portosystemic shunt –> shunts ammonia from the liver, which normally metabolizes ammonia in the urea cycle.

53
Q

What are the clinical findings of encephalopathy?

A

Alterations in mental status.
Somnolence and disordered sleep rhythms.
Asterixis (flapping tremor) –> jerky, irregular flexion-extension movements at the wrist and metacarpophalangeal joints.
Coma and death in late stages.

54
Q

What is portal hypertension?

A

Problem in flow of blood within the sinusoids because of the fibrous tissue accumulating and the regeneration of hepatocytes.

55
Q

What is the pathogenesis of portal hypertension?

A

It is due to resistance to intrahepatic blood flow as a result of compression of sinusoids in the liver from regenerating nodules –> intrasinusoidal hypertension.

56
Q

What are the causes of portal hypertension?

A

Prehepatic resistance –> occlusive thrombosis and narrowing of portal vein.
Intrahepatic resistance –> cirrhosis, schistomiasis.
Posthepatic resistance –> RHF, hepatic vein obstruction, and constrictive pericarditis.

57
Q

What are the complications of portal hypertension?

A

Ascites
Congestive splenomegaly –> increased hydrostatic pressure in splenic vein –> hypersplenism with cytopenia (thrombocytopenia is most common).
Dilation of portosystemic venous shunts –> esophageal varices, hemorrhoids, caput medusae.

58
Q

Esophageal varices is a complication of what type of vascular shunt?

A

Portosystemic shunt.

59
Q

What veins are involved?

A

Azygous vein and left gastric veins.

60
Q

What is ascites?

A

Collection of excess fluid in the peritoneal cavity.

61
Q

What is the pathogenesis of ascites?

A

Increased hydrostatic pressure in portal vein.
Decreased oncotic pressure due to hypoalbuminemia –> leakage of fluid from vascular space.
Secondary hyperaldosteronism due to decreased metabolism of aldosterone by liver.

62
Q

What is the most common cause of nephrotic syndrome in adults and children?

A

Adults –> membranous glomerulonephritis.

Children –> minimal change disease.

63
Q

What are the clinical findings of ascites?

A

Abdominal distention with a positive fluid wave.
Increased risk for spontaneous bacterial peritonitis –> adults (E. Coli) and children (S. pneumoniae)
Fever, chills, abdominal pain, neutrophilic leukocytosis.

64
Q

What is heptorenal syndrome?

A

Appearance of renal failure in patients with severe liver disease in whom there is no other intrinsic causes for renal failure.
Kidney function promptly improves if hepatic function is restored.
Onset is heralded by drop in urine output (oliguria), associated with rising BUN and creatinine values because not getting rid of them in the urine.

65
Q

What is the mechanism of hepatorenal syndrome?

A

Vasoconstriction of renal vessels –> decreased renal blood flow.
Ability to concentrate urine is retained –> produces hyperosmolar urine.

66
Q

What is the cancer resulting in renal failure that is the cause of death in hepatorenal syndrome?

A

Multiple myeloma –> cancer of plasma cells leading to increased synthesis of immunoglobulins –> characterized by Bence Jones proteins and amyloid deposition.

67
Q

What is the pathogenesis of hyperesterinism?

A

Liver cannot degrade estrogen and 17-ketosteroids (eg, androstenedione).
Androstenedione is aromatized into estrogen in the adipose cell.
The total level of estrogen keeps increasing.

68
Q

What are the clinical findings of hyperesterinism in males?

A

Gynecomastia
Spider angiomas (telangiectasia)
Female distribution of hair
Palmar erythema

69
Q

What is the unique thing about hepatocellular carcinoma?

A

Even though it is a carcinoma, it does not spread via the lymphatic route, instead it spreads like sarcomas, via the hematogenous route.

70
Q

What are the laboratory test abnormalities in cirrhosis?

A

Decreased serum BUN and increased serum ammonia –> disruption of the urea cycle.
Fasting hypoglycemia –> defective gluconeogenesis and decreased glycogen stores.
Increased PT (INR) –> decreased synthesis of coagulation factors, including factor VII.
Chronic respiratory alkalosis –> toxic products from hepatic dysfunction overstimulate the respiratory center.
Lactic acidosis –> liver dysfunction in converting lactic acid to pyruvate.
Hypokalemia –> secondary aldosteronism increases renal exchange of Na for K.
Hypoalbuminemia
Hypocalcemia –> decreased albumin to bind to calcium.
Vitamin D deficiency –> vitamin D is not undergoing hydroxylation reaction in liver and therefore not getting activated leading to calcium and phosphate not absorbed in gut.
Mild transaminasemia –> mild increase in AST and ALT.

Path II Block III (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions