Week 12 Digestive Disorders Flashcards
1
Q
Liver diseases
A
- Hepatic circulatory disorders
- Viral hepatitis
- Toxic liver damage (ethanol)
- Eclampsia and pre-eclampsia
2
Q
Gall bladder diseases
A
- Cholestasis
- Cholecystitis
3
Q
Pancreas diseases
A
- Neuroendocrine tumors
* Gastrinoma
* Insulinoma
* Somatostinoma - Diabetes Mellitus (type 2)
- Acute vs Chronic pancreatitis
4
Q
What do hepatocytes of the liver do?
A
- detoxification
- bile production
- blood proteins
- glycogen storage–> to help maintain BG levels b/t meals
5
Q
Parenchyma of liver
A
Hepatocytes
- large cells with lots of organelles
- divide so liver can regenerate
6
Q
Stroma of liver
A
- reticular fibers
- kupffer cells
- eto cells
- endothelial cells
- etc.
7
Q
2 types of liver vasculature
A
- Systemic
- providing support through proper hepatic artery
- high O2 levels - Functional
- from digestive tract through portal vein
- high nutrient levels
8
Q
liver vasculature pathway
A
- blood enters parenchyma (sinusoids)
- drains into central vein
- to sublobular vein
- exits liver through hepatic vein
9
Q
Blood flow through liver (image in ppt)
A
- blood flowing towards central vein
- bile flowing towards periphery
- kupffer cells are resident macrophages of the liver
- portal vein–> brings blood from GI tract into sinusoids
- hepatic artery–> brings O2 rich blood to sinusoids
- central vein–> sublobular vein–> hepatic vein
10
Q
Liver perfusion
A
- parenchyma organized into lobules
- hepatocytes closes to entry receive most nutrients, as well as heaviest dose of toxins
* this is zone 1–> closest to portal triad
11
Q
What are the mechanisms used for liver response to injury?
A
- Hepatocyte-based response
* degeneration/intracellular accumulations
* death- necrosis or apoptosis - Inflammation- often started by kupffer cells
- Regeneration
- Fibrosis- failure of regeneration
12
Q
Name some clinical liver syndromes.
A
- Hepatic Failure
- absence of general functions
- cells do not function properly - Cirrhosis
- architectural disruption
- fibrosis with nodules of hepatocytes
- not always immediately apparent - Portal Hypertension
- increased resistance to blood flow in the liver
- this can induce cirrhosis - Bilirubin metabolism failure
- causes jaundice
- can be a result of cholestasis
13
Q
Fibrosis in the liver
A
Fibrosis is due to activation of stellate cells
- secondary to activation of kupffer cells
- this is how you get cirrhosis
14
Q
Describe Bilirubin
A
- senescent (deteriorate w/ age) RBCs are destroyed by phagocytic cells
- in spleen, liver, and bone marrow
- bilirubin is a yellowish pigment
- seen in fading bruises as RBCs from hemorrhage are removed
15
Q
How does bilirubin travel in the body?
A
-NOT water soluble
- travels through blood bound to albumin
- conjugated to glucuronic acid for excretion in bile–> eventually in fecal matter
* bile salts are recycled, but conjugated bile is excreted
16
Q
What is cholestasis?
A
impaired bile formation/flow
17
Q
What results from excess bilirubin?
A
- jaundice–> yellowing of skin
- icterus–> yellowing of sclera (eye)
18
Q
What is Hepatitis?
A
- Virus that infects hepatocytes
- Liver with hepatocytes infected by hepatitis virus
- Liver damage secondary to systemic infection
Acute Hepatitis: massive hepatocyte damage (necrosis)
Chronic Hepatitis:
- end stage of progressive hepatocyte damage
- liver recovers from initial injury, but then you have additional injuries occuring
19
Q
What are some clinical syndromes associated with hepatitis?
A
- Acute Hepatitis–> with submassive hepatic necrosis
- Asymptomatic
* serological evidence only
* acute with recovery
- Acute symptomatic hepatitis with recovery
* anicteric or icteric (jaundice) - Chronic hepatitis
- with or without progression to cirrhosis
- similar presentation to toxic liver injury - Acute liver failure
- with massive hepatic necrosis
20
Q
Acute vs Chronic Hepatitis
A
Acute
- damage to hepatocytes themselves
* including cholestasis, apoptotic cell death, ballooning degeneration
- proliferation or increased deposition of macrophages of kupffer cells
Chronic
- differences in types of cells present
* lymphocytes
* Hep B= ground glass cells
* Hep C= fatty change
NOTE: acute may have bridging necrosis, but chronic WILL have it
21
Q
Describe Viral Hepatitis
A
- virus infects hepatocytes
- hepatocytes express viral antigens
- immune system targets hepatocytes
22
Q
Causes of hepatitis
A
Acute
- primary viral (hep A,B,C,D,E)
- systemic viral (yellow fever, mononucleosis)
Chronic (the consonants)
- most likely with hep C; minimal with B/D
- E only in immunocompromised
- Never with hep A
- can be follow-up to unresolved acute injury, or result from subacute injury
Usually characterized by cirrhosis b/c you lose hepatocytes during infection and you have fibrosis to replace it
- often linked with hepatocellular carcinoma- b/c of viral infection
23
Q
What causes the ground glass appearance in hepatocytes of Hep B infection?
A
accumulation of HBsAg that cause eosinophilic inclusions that give this appearance
24
Q
Why is Hep C very likely to become chronic?
A
- RNA never cleared from acute infection and then reactivation of endogenous HCV strain
- emergence of new strain
25
What are the consequences of hepatitis?
Loss of liver function b/c losing hepatocytes
- Hypoproteinemia--> b/c hepatocytes no longer producing blood proteins
- Hyperbilirubinemia--> jaundice produced b/c of insufficient bilirubin conjugation/excretion through bile
- Anemia--> due to decreased overall liver function
*fatigue common
* many treatments can cause anemia
Infections/stress cause additional damage
- Cirrhosis may be undiagnosed
26
What are the symptoms of chronic hepatitis?
- fatigue, malaise, loss of appetite, mild jaundice
-blood tests
* serum transaminase is elevated
* hyperglobulinemia, hyperbilirubinemia
- minor hepatomegaly/splenomegaly
- hepatic tenderness
27
What is the treatment for hepatitis?
manage symptoms
28
What can happen with both toxic and viral liver damage?
- produce acute or chronic disease
- can result in an immune response
- result in destruction of hepatocytes (cirrhosis)
29
Why must toxins always be eliminated as a potential cause of liver damage?
b/c the liver is the primary detoxifying organ of the body
- toxins must be eliminated as a cause while also looking for viral damage b/c it is possible someone could have both
30
Why do you get an immune response with liver damage?
- not just the death of the cells
- sometimes exposure to toxins can convert cellular proteins into an immunogen by altering it enough that your immune system will recognize it as foreign
31
Toxic vs Viral Zonal damage to liver
Toxic
- most damage in zone 3 (near central vein) b/c least O2, least supported
- zone 3 not exposed to the most toxin, but most likely to suffer effects from the toxin b/c of lack of support
Viral
- most damage in zone 1 (periphery)
- these cells are most exposed to the virus
32
Name some common liver toxins
Acetaminophen
- conversion to reactive intermediates that can kill the cells
Chlorpromazine--> dopamine antagonist (treats schizophrenia)
- forms insoluble complexes in bile- can cause cholestasis by blocking bile ducts
- metabolites
* inhibit membrane enzymes
* impair cytoskeletal functions
Ethanol
- more complicated
33
Mild vs Serious ethanol injury
Mild
- moderate alcohol intake (6 beers)
- steatosis (fatty deposits form in liver)
- normally cleared, but will accumulate with chronic alcohol intake
Serious
- massive intake or chronic effect
- hepatitis
34
What effects does alcohol have on hepatocytes that it can cause alcoholic hepatitis?
- affects membrane function (chemical)- inserts in the membrane and affects normal fluidity of membrane
- induces/inhibits enzymes that detoxify foreign compounds
- enhances O2 toxicity
- oxidized to acetaldehyde
* inhibits protein export/metabolism
* alters redox potential
NOTE: acetaldehyde is assoc. with alcoholics developing malnutrition
35
What is steatosis?
Fatty deposits form in the liver
36
What is steatofibrosis?
Fatty deposits with fibrosis
- subsequent to activation of stellate cells
37
Interplay of Hepatic Injury
Normal liver
Steatosis
- fatty change
- perivenular fibrosis
Hepatitis
- liver cell necrosis
- inflammation
- Mallory bodies
- fatty change
Cirrhosis
- fibrosis
- hyperplastic nodules
NOTE: all 3 conditions can develop independently and they can happen with other types of liver injury
38
Non-alcoholic fatty liver disease phenotypes (NAFLD)
80% isolated fatty liver
- none to minimal progression to cirrhosis
- no increased risk of death compared with general population
Non-alcoholic steatohepatitis (NASH)
- NASH cirrhosis in 11% over 15 years
* Decomposition in 31% over 8 years
* Hepatocellular carcinoma in 7% over 6.5 years
39
Hepatic vascular disease/ circulatory disorders
Impaired blood flow--> Esophageal varices
- portal vein obstruction
- intra or extrahepatic thrombosis
Impaired intrahepatic blood flow--> esophageal varices; ascites (cirrhosis)
- cirrhosis
- sinusoidal occulusion
Hepatic vein outflow obstruction--> jaundice
- hepatic vein thrombosis
- sinusoidal obstructive syndrome
40
Describe sickle cell disease in the liver.
- sickles can cause occlusion of sinusoids
- impaired intrahepatic blood flow--> obstructing/occluding the sinusoid
- liver damage in sickle cell patients is secondary to occlusion of the sinusoids
41
Prehepatic causes of portal hypertension
- obstructive thrombosis of portal vein
- structural abnormalities such as narrowing of portal vein before it ramifies in the liver
42
Intrahepatic causes of portal hypertension
- cirrhosis from any cause
- primary biliary cirrhosis (even in absence of cirrhosis)
- massive fatty change
- diffuse, fibrosing granulomatous disease (ex: sarcoidosis)
- amyloidosis
43
Posthepatic causes of portal hypertension
- severe right-sided heart failure (cor pulmonale)
- constrictive pericarditis
- hepatic vein outflow obstruction
44
What is pre-eclampsia vs eclampsia
-Sx: maternal HTN, proteinuria, peripheral edema, coagulation abnormalities (hypercoagulability)
- may also manifest as liver disease (HELLP syndrome)
* H= hemolysis
* EL= elevated liver enzymes
* LP= low platelets
* if coagulation is impacted, may be fatal
- hemorrhage into the space of Disse in liver
- fibrin deposits develop in periportal sinusoids (sinusoids closest to portal triads)
- develop coagulative necrosis of hepatocytes
- hematoma may form under Glisson's capsule (thick CT capsule of the liver)
* can lead to catastrophic hepatic rupture if gets large enough
45
What are cholestatic syndromes?
diseases related to the movement of bile, but the damage is w/in the liver
46
What is cholestasis?
Systemic retention of bilirubin and other solutes--> b/c they are excreted by the liver, usually damage is in the liver
- excess cholesterol
- xenobiotics
- other waste products that are not water soluble
Impaired bile formation and flow
- accumulation of bile in hepatocytes
- obstruction of bile channels (extra- or intrahepatic)
- defects in hepatocyte bile secretion
47
What are symptoms of cholestasis?
- jaundice
- pruritis
- skin xanthomas (cholesterol accumulation)
- malabsorption (failure to digest/absorb fat in intestines)
48
What are the 3 mechanisms involved in sepsis causing cholestasis?
1. Direct effects due to infection w/in liver (abscess or cholangitis)
2. Ischemia due to hypotension (esp. if liver is cirrhotic)
3. Circulating microbial products
- most likely to lead to cholestasis, esp. w/ gram-negative bacteria
Most commonly leads to canalicular cholestasis
- bile plugs w/in centrilobular bile canaliculi
- activated kupffer cells
- mild portal inflammation
Ductular cholestasis is more serious
- dilated canals of hering and bile ductules w/ bile plugs
- edema and presence of neutrophils in stroma
- hepatocyte death possible
49
What does the gall bladder do?
stores and concentrates bile
- simple columnar epithelium to absorb water to concentrate the bile
- gall bladder rests under liver
- shares a bile duct
- if bile is not secreted into duodenum, it will back up to cystic duct to be stored in gall bladder
50
What is cholecystitis?
Inflammation of the gall bladder
- may be acute or chronic
- may be both
- almost always assoc. with gall stones
51
Describe acute cholecystitis
- enlarged, tense gall bladder--> produces pain
- wall is thickened and fluid-filled (edematous)
- serosa may have hemorrhages beneath--> hemorrhages in wall of gall bladder
- may be covered with fibrinous exudate on surface of gall bladder
* fibrinosuppurative (pus) is a sign of more severe disease
52
Describe chronic cholecystitis
Mucosal inflammatory infiltrate
- puts a lot of pressure on the wall
- can get large sinuses forming--> disrupts muscularis externa of the gall bladder
Rokitansky-Aschoff sinus
- assoc. with proliferation of epithelial cells
- considered pre-cancerous lesion
53
Name the tumors of the endocrine pancreas
Glucagonoma
Insulinoma
Somatostatinoma
NOTE: all benign tumors
54
What are neuroendocrine tumors?
- <2% of pancreatic tumors; most assoc. with exocrine pancreas
- symptoms relate to excessive hormone release by these benign tumors
- overgrowth of specific cell type
* alpha= glucagonoma
* beta= insulinoma
* delta= somatostatinoma
55
Details of somatostatinoma
- somatostatin inhibits alpha and beta cells
* diabetes--> altered glucose uptake--> due to downregulation of insulin production
* cholethiasis--> impaired bile secretion (gall stones)
* steatorrhea--> impaired exocrine pancreatic excretion (excess fat in fecal matter)
- both cholethiasis and steatorrhea due to lack of glucagon
56
Describe glucagonoma
-overgrowth of alpha cells
- excessive glucose mobilization
- produces hyperglycemia
- patients have characteristic rash
* due to malnutrition
* excessive AA uptake for use as fuel to produce more glucose
57
What is happening with glucose production due to glucagonoma?
- glucagon activates gluconeogenesis, which will use amino acids as fuel to produce more glucose
- instead of using AAs in the body to make proteins, patients will have malnutrition b/c AAs are being used to make more glucose
58
Describe insulinoma
- excess glucose - uptake so glucose levels in blood drop dramatically
- clinically, hypoglycemia producing neurological symptoms (confusion, stupor, loss of consciousness)
- symptoms relieved by food intake or receiving glucose
- precipitated by exercise or fasting--> causes BG levels to drop even faster
59
What is the main difference in classification between type 1 diabetes and type 2 diabetes?
Type 1: beta cell destruction
- usually leading to absolute insulin deficiency
Type 2: combination of insulin resistance and beta cell dysfunction
60
What are the clinical manifestations of diabetes?
- b/c breaking down more adipose tissue, free fatty acids will increase appetite
- protein catabolism in muscle will also increase appetite
- free fatty acids increase ketogenesis, which increases ketoacidosis, which can cause diabetic coma
* ketoacidosis also affects kidneys, producing excess ketones in urine
- hyperglycemia produces glycosuria
- ketoacidosis and glycosuria both increase urine volume by affecting uptake of H2O in collecting ducts
* volume depletion= increased thirst
61
What are the diseases of the exocrine pancreas discussed?
Acute and Chronic Pancreatitis
- inflammation assoc. with damage to exocrine tissue
- acute--> reversible damage
- chronic--> irreversible damage
* can present as repeated incidents of acute damage that do not fully resolve
* losing more tissue with each incident
62
Acute pancreatitis
reversible parenchyma injury with inflammation
63
Common causes of acute pancreatitis
- biliary tract disease
- alcoholism mostly
- toxins
- trauma
- vascular disease
64
Why can biliary tract disease cause acute pancreatitis?
It can affect the pancreas b/c pancreatic secretions go through the same ampulla of otti just like the common bile duct
- any damage along there can affect movement of product from the pancreas
65
What does activation of trypsin have to do with pancreatitis?
- changes assoc. with acute pancreatitis suggest autodigestion of the pancreas by its own digestive enzymes causes initial damage, which then induces inflammatory response
- trypsin is activated in pancreas rather than in the duodenum
- supported by hereditary pancreatitis
* mutation in cleavage site--> fail safe; important for de-activation--> mutation means you cannot deactivate trypsin
* mutation in trypsin inhibitor--> increases risk of irregular activation of trypsin if it's mutated and cannot inhibit trypsin
66
What is the normal activation of trypsin?
Normally, pancreatic enzymes are secreted and go to duodenum, where trypsin is activated
- trypsin then activates most of the other pancreatic enzymes
67
What enzymes are linked to autodigestion of the pancreas?
Microvascular leakage (edema)
- Elastase damages vessel walls
Fat necrosis
- activation of Lipases
Parenchymal degradation
- Proteases (trypsin, chymotrypsin, etc.)
Thromboses damage weak vessels
- Clotting defects
Hemorrhage
- Kallikrein--> type of kinin related to BP and inflammation
* also involves plasma, which degrades clots and activates clotting factors
68
Acute vs Chronic pancreatitis
Both
- acinar cell injury
Acute
- resolution
Chronic
- loss of cells with fibrosis occurring
69
Describe chronic pancreatitis
- Inflammation with irreversible damage to exocrine parenchyma
* irreversible damage= distinction from acute
- eventually, fibrosis develops, and may even impact endocrine parenchyma--> start seeing effects on glucagon, insulin, and somatostatin
- most common cause is long-term alcohol abuse
* increased excretion of pancreatic enzymes--> duct obstruction
* directly toxic to acinar cells
70
Pathogenesis of chronic pancreatitis
Similar to acute
- duct obstruction
- cell injury
Oxidative stress has a role in chronic
Repeated acute episodes
- perilobular fibrosis
- duct distortion
- altered secretion
Results in fibrosis and parenchyma loss
71
Describe clinical pancreatitis
- upper abdominal pain due to inflammation of pancreas
- nausea, vomiting, fever, tachycardia, sweating
- icterus/jaundice--> especially if pancreatitis is caused by obstruction in ampulla of otti b/c you have damage to pancreas and damage to liver and gall bladder as well
72
Treatments for pancreatitis
- IV fluids
- NO food--> food ingestion activates exocrine pancreas
- medicine for pain
