Liver and Pancreas
protein synthesis in the liver
The liver is the site of synthesis of all major plasma proteins except immunoglobulins. *Albumin *Globulins *Clotting proteins
adenocarcinoma
The most common carcinoma of the pancreas
cavernous hemangioma
The most common liver tumor. These are usually small and cause no symptoms.
the pancreas and digestion
The pancreas is anatomically and functionally a part of the digestive tract. A loss of pancreatic cells or inadequate drainage of juices into the duodenum affects digestion.
Pancreatitis
a chemical inflammation of the pancreas, sterile, non-infectious
Autoimmune Hepatitis
a form of chronic hepatitis, thought to be immune mediated because it is associated with other autoimmune phenomena. (has antibodies to smooth muscle) Affects mostly young women.
Cellular changes and apoptosis
affected liver cells have normal nuclei and a well preserved cell membrane but show cytoplasmic changes. Dying liver cells lose their nuclei and are transformed into round, anuclear, cytoplasmic fragments.
Wilson's Disease
aka "hepatolenticular degeneration"-an autosomal recessive disorder of copper metabolism that produces lesions in the liver, brain, and the eyes.
Gilbert's disease
an autosomal dominant disorder of bilirubin metabolism that affects 5% of the total population. Most common in males. Causes intermittent jaundice that usually begins after puberty but requires no treatment. Unconjugated hyperbilirubinemia reflects a defect in the uptake of bilirubin from blood into liver cells.
Hemochromatosis
an autosomal recessive defect of iron absorption that results in excessive accumulation of iron in the liver and several other organs. Also called "pigmentary cirrhosis"
Inflammatory response
damages and dead liver cells are phagocytized by macrophages that invade the liver lobule, forming small foci within the disrupted strands of liver cells. Can be mild like in Hepatitis A or more extreme like in Hepatitis C (scarring).
Cirrhosis
end-stage liver disease - a chronic liver disease characterized by a loss of normal liver structure and function. It is irreversible and incurable except by liver transplantation. -it is characterized by fibrosis and regenerating liver cell nodules that replace the normal parenchyma. There is scarring and has fibrous formation. -The cells can no longer function as a normal liver cell.
acute pancreatitis
expect to see swelling, hemorrhagic -Caused by: Obstruction of the pancreatic duct, Chemicals put into the pancreatic duct, Surgical or mechanical overstimulation of pancreatic cells (acini) -Linked with alcohol overuse, gall stones, Symptoms include pain, nausea, vomiting, also causes regional problems
the pancreas
head, body, tail, single pancreatic duct in the middle, many ductules throughout, the pancreatic duct meets with the common bile duct to empty into the ampule of Vader into the duodenum. *Principal hormones secreted: -Insulin - secreted by beta cells!!! -Glucagon
Newly formed hepatocytes
liver cells have a high capacity for regeneration, and any loss is usually accompanied by regeneration, which occurs at random. The newly formed liver cells are relatively smaller and have more basophilic cytoplasm.
chronic pancreatitis
looks like a fibrosis of the tissue, is whitish in color, is progressive and irreversible, has an insidious onset, asymptomatic in the beginning, when symptoms do show, have enzyme insufficiencies
Primary Sclerosing Cholangitis
may have immune pathogenesis. Predominantly affects young men. Fibrosis obliterates the bile ducts inside and outside the liver.
Diabetic neuropathies
pain and numbness
Exocrine functions of the pancreas
production of digestive enzymes (98% of its function) acini cells produce important enzymes (amylase, peptidase, lipase) and release the into the ductal system in an inactive form.
liver tumors
rarer to get a primary tumor in the liver, more common to get mets in the liver
Intracellular viruses
release toxins causing apoptosis, inflammation - (severe in hep C, leads to cirrhosis & scarring
Diabetic stroke
stroke due to vascular effects in the brain
Insulin
the most important hormone secreted by the pancreas. A deficiency in insulin can cause diabetes. Hormone imbalance between insulin and glucagon can be an issue.
Islet cell tumors
tumors within islet cells- (insulinomas) typically beta cells, causes the beta cells to produce too much insulin, can be treated with glucose
Diabetic nephropathies
vascular disease and more prone to infection
Diabetic retinopathies:
vascular disease in the retina, glaucoma, cataracts
Drug-Induced Liver Disease
—the liver is the primary site for the metabolic conversion and inactivation of drugs and various toxins. In this process, the liver cells may be injured by the chemical that is metabolized or by the toxic derivatives formed inside the liver cells. Overuse of the liver in processing the drug toxins leads to disease.
Complications of Cirrhosis
•Ascites: fluid accumulation in the abdomen •Splenomegaly: enlargement of the spleen •Portal hypertension and esophageal varices: *the esophageal region = varicosities *rectal region = hemorrhoids *anterior abdominal wall varices * Massive hemorrhage is one of the most common causes of death in patients with cirrhosis.
Functions of the liver:
•Bile production •Stores fats and carbs •Processing nutrients •Protein synthesis •Blood detoxification
Primary Biliary Cirrhosis
(PBC) unknown etiology, characterized by destruction of intrahepatic bile ducts and progression to cirrhosis. (resembles T-cell mediated destruction of bile ducts associated with transplants and graft-vs-host disease. Predominantly affects women.
Diabetes mellitus - Type II
(adult-onset: NIDDM): This reflects the body's attempt to compensate for the deficiency of insulin.
Jaundice
(is a symptom, not an actual disease) get yellowing discoloration of the skin and mucosa, always due to increased bilirubin in the blood (hyperbilirubinemia) -classified as conjugated, unconjugated, or mixed
Diabetes mellitus - Type I
(juvenile): IDDM- caused by destruction or loss of the beta cells, results in an insulin deficiency.
Normal Structure of the Liver
*4 lobed structure: right, left, caudate (next to IVC), quadrate (next to gallbladder) *Composed of liver cells known as hepatocytes (90% of total mass) other cells are bile ductile cells and vascular cells lining sinusoids and vessels. *Hepatocytes are arranged into functional units called lobules *Gallbladder on inferior surface *Dual blood supply
Hepatitis B
*DNA virus, Symptoms usually appear 40 to 180 days after infection. *Infection follows transfusion of blood, exposure to contaminated blood or blood products, or sexual contact. *The disease has three phases: preicteric, icteric, and convalescent. *In the preicteric phase there is weakness, nausea, vomiting, and jaundice. *This disease CAN TRANSITION INTO CHRONIC HEPATITIS.
Hepatitis C
*RNA virus, is transmitted via blood and is often acquired by blood contaminated needles used during intravenous drug abuse. *Other risk factors are multiple sex partners, surgery, and accidental needle stick or scalpel injuries. *symptomology is less severe, but disease does become chronic in 50% of affected people *CAN TRANSITION INTO CHRONIC HEPATITIS.
Hepatitis A
*RNA virus, transmitted by the fecal-oral route, and it may occur in sporadic or epidemic form. *The sources of the virus are sewage, contaminated food and drinks, and shellfish. *Symptoms usually develop after a short incubation period of 15-50 days. *Symptoms include: enteric fever with vomiting, loss of appetite, and jaundice. *Recovery occurs within days, usually without any long-term consequences. *DOES NOT TRANSFER INTO CHRONIC HEPATITIS OR CIRRHOSIS
Hepatocellular Carcinoma
*most important primary liver tumor* -highly malignant -composed of neoplastic liver cells -Etiology: cirrhosis or inflamed liver; occurs in adults, males more than females -Pathology: can show up many different ways: diffuse, infiltrated lesion, solitary mass limited to one lobe, multiple nodules *clinical features include weight loss, appetite loss, and nausea *With primary tumors = expect to see solitary to diffuse*
hepatic portal vein
- (venous blood that is O2 poor but nutrient rich) -It drains the organs of digestion including the spleen.
Hepatic *conjugated hyperbilirubinemia & unconjugated hyperbilirubinemia*
- due to abnormal processing of bilirubin - when sick or dying liver cells are not able to conjugate (bind) the bilirubin, the unconjugated bilirubin causes jaundice, not all are sick/dying some are still working = mixed cause • Viral/Alcohol/drug overuse is the cause - can lead to hepatitis and cirrhosis
Metabolic function related to digestion
- the portal system is a low pressure venous system, has a low pressure tolerance, normally not connected in any way to the systemic system, but there are anastomoses between portal blood and systemic blood, those anastomoses are usually closed down. However, with cases of liver disease, the anastomoses can open up which results in Portal Hypertension
hepatic artery
-(arterial blood that is O2 rich but nutrient poor)
Immune Disorders
-Autoimmune Hepatitis -Primary Biliary Cirrhosis -Primary Sclerosing Cholangitis
Pancreatic Adenocarcinoma
-Etiology: not well known, old age, alcohol, smoking, drug use, diet -Pathology: mainly arise in the duct system, tend to be in the head of the pancreas, if in the head, lends well to blocking the biliary system. -Clinical symptoms are non-specific like that of neoplasia. -Like to metastasize a lot, go to liver, lungs, bones *High mortality!!!*
Hereditary Diseases of the Liver
-Gilbert's disease -Hemochromatosis -Wilson's Disease -Alpha 1-Antitrypsin Deficiency
Diabetes mellitus - cardiovascular effects
-atherosclerosis in coronary vessels and peripheral vessels, gangrene in the feet, diabetic ulcers in the feet, ALL has to do with poor circulation
Gallstones
-bile can form gallstones. Gallstones are formed from the normal components of bile. These stones can cause obstruction or inflammation and are the most important cause of pathologic changes in the biliary tract.
Prehepatic (hemolytic) *Unconjugated hyperbilirubinemia*
-due to abnormal excessive formation of bilirubin secondary to hemolysis, caused by unconjugated bilirubin -Hemolysis of RBCs (RBC destruction) & hemolytic anemias -Hematoma (bruises) **Malaria is the most common cause of hemolytic jaundice.
Posthepatic (obstructive) *Conjugated hyperbilirubinemia*
-due to abnormal excretion of bilirubin, caused by conjugated bilirubin, typically caused by an obstruction of bile flow, usually at the level of the common bile duct *Anything that can cause a blockage or obstruction of the bile ducts => jaundice *lodged gall stones *tumors -the bile does not reach the intestine and the feces appear clay colored or tan; associated with steatorrhea *Obstructive jaundice is an important symptom of carcinomas involving the head of the pancreas.
Hepatic veins
-empty directly into IVC. There are two ways in the liver but only one way out.
Bile
-made in liver, stored in gallbladder -emulsifies fat in the duodenum -enters duodenum via common bile duct (ampulla of Vader) and is then mixed with food, pancreatic, and intestinal enzymes.
Albumin
-plasma protein that regulates oncotic pressure in blood -Lack of albumin reduces the oncotic capacity of the plasma, resulting in edema.
Metastasis to the Liver
-secondary liver tumors are much more common than primary liver tumors -These metastases, which reach the liver through the portal or arterial circulation, are most often related to primary tumors of the GI tract, lungs, and breast. -Metastases are the most common causes of hepatic enlargement. -Jaundice, ascites, and splenomegaly are common symptoms.
Pancreatic Neoplasms
1. Endocrine tumors: (rare, hormone secreting tumors, not severe) -Islet cell tumors -Diabetes mellitus 2. Pancreatic Adenocarcinoma
2 consequences if anastomoses open up & blood bypasses the liver:
1. it is not detoxified and can have deleterious effects on other organs 2. it will not pick up the albumin, globulin, or clotting factors from the liver
Hepatitis Viruses in general
All hepatitis viruses produce similar changes in the liver. They are hepatotropic and invade liver cells, damaging them and disrupting their normal functions and finally promoting cell death by apoptosis. *with chronic hepatitis, liver will become cirrhotic
Clinical Features of Jaundice:
Bilirubin, conjugated and unconjugated, binds to connective tissue and stains it yellow. It is best seen on the sclera, which is normally white. The unconjugated bilirubin is bound to albumin, thus it does not cross the BBB and does not appear is CSF or in the brain or in urine. However, conjugated bilirubin, which is water soluble, is excreted in urine. The urine may appear brown.
Alcohol Liver Disease
Chronic alcohol abuse may cause hepatic lesions, Fatty liver, Alcohol hepatitis, and cirrhosis. Overuse of the liver in processing the alcohol toxins leads to disease.
Bilirubin metabolism in the blood
In the blood: bilirubin binds albumin, this forms *unconjugated bilirubin* (is not water soluble!) It must then go to the liver to get conjugated (binds to glucuronide in the liver cells) Bilirubin bound to glucuronide becomes *conjugated bilirubin* (is water soluble.) *Must be water soluble before can be excreted in bile. *This process also happens in the spleen.
Bilirubin metabolism in the liver
In the liver, there is a breakdown of RBC: a heme and a globin molecule are produced, heme is bound to iron, but when heme is separated from globin, the iron falls off of heme, bilirubin is what results. (gives bile a yellow hue).
Portal Hypertension
Increased pressure in the portal system causing blood to bypass the liver. This widens the venous channels connecting the portal and systemic circulation, and can also cause varices in the esophageal region, in the hemorrhoidal venous plexus of the rectum, and in the umbilical venous plexus of the anterior abdominal wall, these varices are prone to rupture and tend to bleed profusely.
premature activation of proenzymes
Pancreatic juice contains inactive proenzymes that are activated in the intestine. Premature activation can cause self-digestion of the ducts or tissues. It is very difficult to interrupt their destructive action, so enzyme autolysis may occur.
Pathogenesis of Cirrhosis
Portal (alcohol or viral etiology) or Biliary type (due to disease process of the biliary system) 1) Necrosis: destruction of the liver cells themselves due to continuous exposure to toxins, no longer able to regenerate 2) Fibrosis: then fibrosis, the body is trying to repair the liver cells but the result is scarring and non-functioning liver cells 3) Regeneration: some regeneration in normal tissue, but it can't keep up with the destruction so the liver becomes cirrhotic
Neoplasms
Primary tumors of the liver may be benign or malignant. Benign tumors of the liver and the biliary tract are of limited clinical significance. Malignant tumors can originate from epithelial cells of the liver, bile ducts, and gallbladder.
Endocrine
(2% of function) arranged into islets of Langerhans (Alpha, beta, and delta cells)
Alpha 1-Antitrypsin Deficiency
(AAT) autosomal recessive disorder relate to the presence of the PiZ allele of the gene that encodes for AAT. A significant number of affected people develop childhood cholestasis and chronic hepatitis which eventually progresses to cirrhosis.
Cholelithiasis
(Gallstones) Cholesterol stones: there is a lot of cholesterol in bile, these stones can cause obstruction. -Seen in obese patients, pregnancies, etc. -more dominant in females -Mainly asymptomatic *The Four F's: Female Forty Fertile Fat
