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525 patho final exam


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What is the exocrine function of the liver?
It produces bile, emusifies fats, excreted into a duct.
What is the endocrine function of the liver?
It produces somatomedin C (IGF-1), stimulates growth hormone and growth of bone.
What is the storage function of the liver?
It stores glycogen (storage form of glucose) and iron for synthesis of new hemoglobin.
What is the synthetic function of the liver?
It makes albumin and all other plasma proteins (such as the coagulation proteins), except immunoglobulins.
What is the metabolic function of the liver?
-removes carbs, lipids, proteins from the blood and processes them for use
-removes substances from the blood and breaks them down
-removes circulating hormones from the blood
What are examples of the substances that the liver removes from the blood and breaks down?
-antigen-antibody complexes
-circulating inflammatory mediators
-drugs and toxins
-GI derived ammonia
-hormones (like estrogen)
How do we know if the liver has been injured?
Hepatocytes release enzymes and they appear in the blood. These enzymes are elevated in the serum:
SAST - serum aspartate aminotransferase
SALT - serum alanine aminotransferase
What is jaundice?
The abnormal formation, processing or excretion of bilirubin (a symptom, not a disease).
What are the characteristics of jaundice?
-yellow skin, mucosa, sclera of eyes
-caused by hyperbilirubinemia
-bilirubin binds to connective tissue (makes it yellow)
What is hyperbilirubinemia?
-too much bilirubin in the serum, usually >3 mg/dl.
Classified 3 ways: conjugated, unconjugated, mixed.
What is bilirubin?
It is the breakdown product of hemoglobin.
What causes jaundice?
This is caused by:
-too much hemoglobin is being broken down; or
-when the liver fails to process the bilirubin.
What is icterus?
The yellow skin associated with jaundice?
What normally happens to bilirubin?
Normally, the liver metabolizes this and excretes it as a component of bile.
How is jaundice classified?
This is classified according to the initiating cause of the hyperbilirubinemia.
Prehepatic Jaundice
aka: hemolytic jaundice
"injury before the liver"
In a large hematoma, breakdown of red cells occurs with release of bilirubin, if bilirubin becomes systemic - this occurs (seen in trauma victims).
Hepatic Jaundice
aka: intrahepatic jaundice
"liver damage"
resulting from liver disease;
liver fails to take up normal circulating bilirubin (ex: cirrhosis);
jaundice results when blood levels reach 3 mg/dl
Posthepatic Jaundice
aka: obstructive jaundice
Usually this involves the inability of the liver to get rid of bile, as with gallstones or a tumor blocking the bile duct;
liver can't release bilirubin as a component of bile and it releases it back into blood instead.
What is conjugated bilirubin?
This is joined with gluconeride in the hepatocytes. Associated with obstruction of the biliary system (stones). Posthepatic.
What is unconjugated bilirubin?
This is caused by excessive hemolysis. Prehepatic.
What is mixed bilirubinemia?
This is associated with liver cell necrosis and destruction of liver parenchyma. Hepatic.
What is brown, foamy urine a symptom of?
Viral Hepatitis
-conjugated bilirubin is water soluble and is excreted in urine.
Is unconjugated bilirubin water soluble?
No - it will not be seen in CSF or urine.
Disorders that lead to prehepatic jaundice.
-Hemolytic blood transfusion reaction
-Hereditary disorders of the red blood cell (sickle cell, Thalassemia, Spherocytosis)
-Aquired hemolytic disorders
-Hemolytic disease of the newborn
-Autoimmune hemolytic anemias
Disorders that lead to hepatic (intrahepatic) jaundice.
-Decreased bilirubin uptake by the liver
-Decreased conjugation of bilirubin
-Liver cell damage (hepatitis, cirrhosis, cancer)
-Drug induced cholestasis
Disorders that lead to posthepatic jaundice.
-Structural disorder of the bile duct
-Congenital atresia of the extrahepatic bile ducts
-Bile duct obstruction by tumors
What is fatty liver?
Alcoholic liver disease characterized by infiltration of hepatocytes by fat or lipid material; reversible, does not affect biochemical function of hepatocytes until well advanced. (alcholism is not the only cause)
What causes alcoholic liver disease (fatty liver)?
Metabolism of alcohol (ethanol) by the liver results in increased NADH and decrease NAD.
ethanol+NAD -->/<-- NADH+H+acetaldehyde;
acetylCoA+NADH -->/<-- fatty acids+NAD
-net result,liver is overwhelmed with fatty acids
What are other causes of fatty liver?
-decreased fatty acid oxidation and decreased export of lipioproteins from the liver
-diets high in fat can overwhelm the ability of the liver to process fat (foie gras)
What are esophageal varicies?
Tortuous, highly dilated veins in the esophagus that can hemorrhage; caused by HTN in the hepatic portal system.
What is the hepatic portal system?
The venous drainage from the entire GI tract.
What is a portal system?
Connection of 2 capillary beds:
In a portal system, blood leaves the heart, circulates through arterial system and arrives at a capillary bed in the GI system --> venous drainage continues to the liver where another capillary bed is encountered within the liver --> the liver is then drained by a vein that leads back to the heart.
Is the hepatic portal system low or high pressure?
Low pressure (5-10 mmHg).
What is hepatic portal system HTN?
Liver becomes diseased --> flow of portal blood is impeded --> pressure increases (>12 mmHg).
-Symptoms of this dysfunction are related to the structural connections that exist between this portal system and systemic circulation.
What are the consequences of hepatic portal HTN?
With increasing pressure, anastomoses, normally not functional, become functional --> causes portal and systemic blood to mix (not good).
What are anastomoses?
Venous connections between hepatic portal system and systemic circulation (nonfunctional at normotension).
Where are the anastomoses?
-rectal/anal junction
-esophagus/stomach junction
-part of the stomach
-anterior abdominal wall
What are some symptoms of hepatic portal HTN?
Caput medussae, hemorrhoids, esophageal and gastric varicies.
What is a dangerous pathological condition that results from hepatic portal HTN?
Mixing of systemic and portal blood allows substances in portal blood to mix with systemic blood without first being filtered by the liver. These substances can be toxic.
In hepatic portal HTN, what happens if ammonia reaches systemic circulation without being removed by the liver?
Ammonia, a normal byproduct of digestion, is very toxic to the brain if it reaches systemic circulation --> hepatic coma or hepatic encephalopathy.
-liver becomes diseased --> liver obstruction --> portal HTN --> anastomoses functional --> ammonia reaches syst. circulation --> hep. coma or encephalopathy
With advanced liver disease there is a decrease in the systemic circulation of substances normally secreted by the liver. What would these be?
-clotting factors

SEE PAGE 935, fig. 40-13, mechanisms.
How would decreased clotting factors from liver disease manifest?
bleeding varicies, hemorrhoids, etc.
How would decrease albumin from liver disease manifest?
As Edema
portal HTN and increased pressure in peritoneal capillaries AND decreased albumin --> decreased oncotic pressure in blood --> ascities
Advanced liver disease also can lead to an enlarged spleen - why?
Portal HTN --> shunting of blood into splenic vein --> splenomegaly and hypersplenism from prolonged transit time of blood through the spleen
-hypersplenism - decreased life span and decrease in number of blood cells, leading to anemia, thrombocytopenia, leukopenia
So, the major complications of portal HTN and opening of collateral channels are:
-formation of portosystemic shunts - anastomoses
Normally the liver removes estrogen. What happens if the liver cannot remove it?
Males - gynecomastia, alopecia, testicular atrophy
Women - menstrual irregularities
What are the three catgories of portal HTN?
What causes posthepatic portal HTN?
Severe right-sided heart failure
What causes intrahepatic portal HTN?
Blockage of blood flow within the liver (Cirrhosis and fatty liver)
What causes prehepatic portal HTN?
Blockage of blood flow to the liver (Splenomegaly,tumor formation)
What is cholestasis?
Biliary blockage [posthepatic] [100% conjugated]
-both intrahepatic and extrahepatic blockages can occur
-adverse affects of digestion of fats and fat-soluble vitamins due to a lack of bile can lead to jaundice
What is the type of jaundice associated with cholestasis?
Obstructive Jaundice
Obstructive Jaundice is also often seen with this disorder:
Carcinoma of the head of the pancreas
Biliary blockage of the duct can result in this:
Reflux of bile back into the pancreas --> pancreas digests (emulsification of fat in cells by bile)
What is cholelithiasis?
Gallstones - concretions composed of chemicals normally found in the bile
Risk factors - 4F's: female, fair-skinned, over 40, Fat
What are gallstones normally composed of?
75% of all gallstones are cholesterol stones
What are the clinical features of cholelithiasis?
-frequently asymptomatic
-inflammation of the gallbladder due to mechanical injury - VAGUE or DULL PAIN
-obstruction of cystic duct - SEVER PAIN due to distension
-JAUNDICE - [posthepatic] [100% conjugated]
What do gallstones predispose a patient to?
Carcinoma of the gallbladder - cell injury causes chronic inflammation --> unwanted cell proliferation.
The liver is the primary site for:
metabolic conversion and inactivation of drugs and toxins.
How does metabolism of drugs and toxins damage the liver?
-DIRECTLY- damage by the compound (ex: phalloidin-toad stools - inhibits RNA polymerase which reads and makes MRNA for protein synthesis
-INDIRECTLY- derivatives of a compound can cause damage (ex: CCCl4, tylenol)
What is cirrhosis?
A chronic liver disease characterized by a loss of normal liver structure and function.
-end stage disease
-irreversible and incurable
-fibrosis (scarring) and liver cell nodules replace normal architecture
What is the etiology of cirrhosis?
-alcohol abuse, HBV, HCV infections account for 65% off all cases of cirrhosis in the US
-30% unknown causes
-hereditary metabolic diseases, autoimmune diseases, drugs, biliary obstruction account the rest
What is the pathogenesis of cirrhosis?
Caused by many years of recurring bouts of necrosis of liver cells and repair by fibrosis with disorganized regeneration of liver cells.
-nodular pattern of liver
-Dx grossly by liver's appearance
-whole liver or regions can be affected
The primary malignancy of the liver:
hepatocellular carcinoma
-can originate in any liver cell
1 million deaths annually worldwide
-common in far east and africa
-S&S weight loss, pain, resembles cirrhosis
-2% of cancer deaths in US
What causes hepatocellular carcinoma?
-consumption of aspergillis flavis-aflatoxin from a fungus that grows on improperly stored (wet) grain
-also seen where HepB virus is endemic
-primary site of metastasis from other cancers
What is the link between cirrhosis and cancer?
Link between cirrhosis and hepatocellular cancer: unwanted cell proliferation.
-highest incidence in cirrhosis secondary to HBV or HCV
What is the link between hepatitis and cancer?
Link between hepatitis and hepatocellular cancer: unwanted cell proliferation.
What are the clinical features of hepatocellular carcinoma?
-nonspecific weight loss, loss of appetite, nausea
-enlarged, tender liver
-portal HTN
-5 yr. survival rate is 10%
-chemo. is ineffective
Why is chemotherapy ineffective with hepatocellular carcinoma?
Because the liver metabolizes chemotherapeutic agents, chemo. will kill patient before it kills cancer cells in the liver.
What are causes of secondary liver tumors?
Metastasis from other cancers - primary tumors of the lung, breast, GI (colon).
-multiple round lesions will grow with necrotic centers
-cells resember ORIGINAL TISSUE
What are the clinical features of metastatic liver cancer?
-liver enlarged and tender
-jaundice, ascites, splenomegaly
-poor prognosis
-death is 6 mos. after Dx
What is viral hepatitis?
A disease caused by inflammation of the liver from infection by 5 viruses.
-often asymptomatic
What is Hepatitis A Virus(HAV)?
-RNA virus (r/t polio)
-15-50 day incubation
-followed by acute jaundice
-fecal-oral transmission
-sources: sewage, contaminated food/drink, sushi, shellfish, poor hygeine
Who contracts HAV?
-common in children in underdeveloped countries
What are symptoms of HAV?
rapid recovery
favorable prognosis
relatively mild symptoms
Is there a chronic or carrier state with HAV?
Is there a vaccin available for HAV?
What are lab markers for HAV?
-elevated SAST(liver specific) and SALT(other cells release this, too) during acute phase (liver cells relsease these enzymes when damaged)
-elevated serum antibodies: IgM-antiHAV then IgG-antiHAV
What does it mean if IgM and IgG specific antibodies are elevated for months after symptoms have gone away?
This means virus is still present and the immune system is still defending the body against it.
What is Heptatitis B Virus (HBV)?
-many phased, serious disease
1)subclinical - evidence of the disease without manifest symptoms - Recovery
2)acute infection - Recovery
3)fulminant - followed by death (entire liver is destroyed)
4)heathy carrier
5)chronic non-progressive or persistent infection in which the patient recovers or moves to next step
6)chronic active that progresses to cirrhosis or hepatocellular carcinoma and death (fibrosis and liver is destroyed)
What are lab markers for HBV?
-First, Serum IgM-antiHBV
-then, Serum IgG-antiHBV
** persistence of IgG-antiHBV may be the only serological indication of viral infection in persistent infection or in a healthy carrier - MAY PERSIST FOR LIFE
The failure to produce antibodies to HBV will lead to what?
Patient cannot clear the virus and will develop chronic active hepatitis.
Is there a chronic or carrier state with HBV?
5-10% become carriers with no physical evidence of disease but can infect others
(only indication may be elevated serum IgG-antiHBV)
Is there a vaccine available for HBV?
Can a person with HBV ever give blood?
What are the clinical features of HBV?
-DNA virus
-40-180 day incubation
-transferred: blood, exposure to blood or blood products, sexual
In HBV profound jaundice is a better clinical outcome than mild jaundice!
In HBV profound jaundice is a better clinical outcome than mild jaundice!
This develops in 1% of patients with HBV:
Acute fulminant hepatitis
- rapid course
- massive necrosis of liver
- death
Can a chronic state develop with HBV?
Yes - smouldering or persistent infection followed by recovery
-develops in <10%
-asymptomatic in 75%
-25% develop chronic active hepatitis and may progress to cirrhosis
Chronic hepatitis has a strong correlation with:
This has a strong correlation with rare development of hepatocellular carcinoma (unwanted cell replication).
What is hepatitis D Virus (HDV)?
-incomplete RNA virus
-requires HBV for replication
can occur simultaneously or as a superinfection following HBV
What characterizes HDV from HBV?
-more severe symptoms
-progression to cirrhosis is more accelerated
What is Hepatitis C Virus (HCV)?
-RNA virus
-acquired by blood transfusion or sexually
What is the clinical presentation of HCV?
-similar to HBV
-acute phase is less severe than HBV
-UNLIKE HBV, may smoulder for years with no symptoms
-UNLIKE HBV, tends to progress to chronic hepatitis (50%) and half of these patients develop cirrhosis
What are lab markers of HCV?
-serum IgM-antiHCV and serum IgG-antiHCV present throughout course of disease
What differentiates HCV from other hepatitis infections?
-higher incidence of hepatocellular carcinoma
-liver enzymes remain elevated throughout course of disease
Is there a vaccine for HCV?
-significant public health concern
What is Hepatitis E Virus (HEV)?
-RNA virus
-fecal-oral transmission
-resembles HAV
-usually asymptomatic and transient symptoms
Who is HEV especially dangerous to?
pregnant women - high mortality
Do chronic hepatitis and chronic carrier states develop with HEV?
Is it possible to differentiate types of hepatitis virus infection histologically?
No - it is impossible to distiguish one from another morphologically.
Where is the pancreas located?
Retoperitoneally in the upper abdomen on the left (behind the peritoneum).
-disease associated with pancreas causes referred pain to the back.
What are the digestive enzymes produced by the exocrine pancreas?
peptidases - trypsin, chymotrypsin
Enzymes of the pancreas are secreted as:
-they become activated by enteropeptidases and increased pH in the duodenum
What are the major diseases of the pancreas?
What is pancreatitis?
Acute or chronic inflammation of the pancreas; usually a sterile chemical inflammation (no pathogens).
-tissue destruction is caused by digestive enzymes released
What is a very mild form of pancreatitis and rarely diagnosed?
Acute edematous pancreatitis
What is a serious form of pancreatitis with a high mortality rate?
Acute hemorrhagic pancreatitis
The premature activatio of pancreatic enzymes results in:
autodigestion of the pancreas
What are three conditions that can cause acute pancreatitis?
1)obstruction of main pancreatic duct, frequently by gallstones with reflux of bile
2)injection of bile or other chemicals into the pancreatic duct
3)mechanical disruption of the pancreatic acinar cells (seatbelt trauma)
What is the pathology of acute hemorrhagic pancreatitis?
-massive edema, hemorrhage, and necrosis of tissue
peritoneal irritation or chemical peritonitis occurs due to leakage of enzymes
-serum levels of lipase and amylase are high
What are the clinical features of acute hemorrhagic pancreatitis?
-sudden onset
-seen in patients w/gallstones or alcoholism
-SEVERE abdominal pain - distension, nausea, vomiting (ACUTE ABDOMEN)
-elevated serum amylase, lipase
What is the treatment for acute hemorrhagic pancreatitis?
No effective treatment - efforts are spent containing the damage and preventing shock
-20-50% mortality rate
Patients who survive an attack of acute hemorrhagic pancreatitis are at risk for what?
Risk for recurrence, progression to chronic pancreatitis.
What is chronic pancreatitis?
Normal parenchyma is replaced by irregular fibrosis after repeated bouts with inflammation.
-irreversible due to tissue destruction
-results in endocrine and exocrine insufficiency
What are some causes of chronic pancreatitis?
-cystic fibrosis
-acute pancreatitis
What other disorders can result after development of chronic pancreatitis?
-Diabetes Mellitus
-Risk for adenocarcinoma of pancreas - at tail of pancreas (by the time symptoms are noticed, it is too late - 0% 2 year survival rate)
What are factors that can lead to chronic pancreatitis?
-alcohol abuse
-high fat diet
*usually affects people >40
What are the clinical symptoms of chronic pancreatitis?
-often asymptomatic or vague symptoms
-back pain
-late in disease - jaundice due to biliary blockage
-digestive problems due to blockage of pancreatic duct

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