Lectures 17 & 18 - GI Pathophysiology III & IV Flashcards
1
Q
What is the largest organ in the body?
A
Liver
2
Q
Blood supply of liver?
A
- Hepatic artery
2. Portal vein
3
Q
O2 saturation in the portal vein?
A
60-70%
4
Q
Functional unit of the liver?
A
Lobule
5
Q
Shape of lobule?
A
Cylindrical
6
Q
Number of lobules in liver?
A
50,000 - 100,000
7
Q
Describe the organization of a liver lobule.
A
- Organized around a central vein that empties into the hepatic vein, and then to the vena cava
- Terminal bile ducts (from caniculi) and small branches of the portal vein and hepatic artery are located in the periphery
8
Q
Can liver lobules be regenerated?
A
YUP
9
Q
Lining of blood supply in liver lobule?
A
Less than 2 hepatocytes thick
10
Q
What are Kupffer cells?
A
Cells between endothelial cells (incorporated into lining) of liver sinusoids that are resident macrophages for surveillance and response and play a large role in the recycling of RBCs
11
Q
Other name for Kupffer cells?
A
Stellate macrophages
12
Q
What are stellate cells?
A
Cells between endothelial cells and hepatocytes that store lipids and vitamin A as retinyl esters and are fibrotic (make collagen and ECM when activated)
13
Q
What % weight of the liver to the stellate cells comprise?
A
5%
14
Q
When do stellate cells lay down fibrotic tissue? Consequences?
A
When they go from quiescent state to activated
Consequences:
- Diffusion of nutrients from liver sinusoids to hepatocytes is impaired
- Increased pressure in liver sinusoids and veins => damage to hepatocytes
15
Q
7 functions of liver?
A
- Regulation of carbohydrate, lipid, and protein metabolism
- Regulation of cholesterol production
- β-oxidation of fatty acids
- Endocrine functions: secretion of angiotensinogen and insulin-like growth factor 1 (IGF1), steroid hormone metabolism
- Detoxification
- Vitamin and iron storage
- Bile production
16
Q
What do the half-lives of steroid hormones depend on? What does this mean?
A
Liver function
The plasma levels of these hormones increase when the liver fails
17
Q
Purpose of bile?
A
Critical for transport of lipids through the unstirred water layer to the enterocytes
18
Q
What does bile contain?
A
- Water
- Bile salts
- Bilirubin
- Cholesterol
- Others
19
Q
What is cholestasis?
A
Decrease in bile flow through the intrahepatic canaliculi causing materials normally transferred to the bile (bilirubin, cholesterol, and bile acids) to accumulate in the blood
20
Q
Symptoms of cholestasis? Which is most common?
A
- ***Pruritus
- Skin xanthomas
- Nutritional deficiencies of fat-soluble vitamins: A, D, K
21
Q
What does pruritus mean?
A
Itching of the skin due to high cholesterol
22
Q
What are skin xanthomas?
A
Fatty growths underneath the skin
23
Q
What happens to the bilirubin once it is transported by albumin to the liver?
A
Conjugated by liver => secreted in bile => gallbladder => small intestine => conjugated bilirubin turned into urobilinogen => excreted in feces (mainly) and reabsorbed to be placed into bile again or excreted by the kidneys
24
Q
What is jaundice? 4 causes?
A
Abnormally high accumulation of bilirubin in the blood
Causes:
PREHEPATIC JAUNDICE
1. Excessive hemolysis (destruction of RBCs)
INTRAHEPATIC JAUNDICE
2. Impaired uptake of bilirubin by the liver
3. Decreased conjugation of bilirubin
POSTHEPATIC JAUNDICE
4. Obstruction of bile flow between liver and intestine
25
5 common causes of prehepatic jaundice?
1. Hemolytic blood transfusion
2. Sickle cell anemia
3. Hemolytic disease of newborn
4. Autoimmune hemolytic anemia
5. Dyserythropoiesis
26
3 common causes of intrahepatic jaundice?
1. Hepatitis
2. Cirrhosis
3. Cancer of the liver
27
3 common causes of posthepatic jaundice?
1. Strictures of the bile duct
2. Gallstones
3. Tumors of the bile duct or near the bile duct (e.g. pancreatic cancer, duodenal cancer)
28
How to tell the difference between pre/intra and posthepatic jaundice?
Increase in conjugated bilirubin levels will be seen in POSThepatic jaundice ONLY
29
2 types of hemolytic disease of newborn?
1. Normal: immature hepatocytes and short RBC half-life
2. Abnormal: newborn blood type is different from mother's blood type (especially Rh difference) and the birth process causes many maternal antibodies to enter the newborn's bloodstream
30
3 types of portal HT?
1. Prehepatic
2. Posthepatic
3. Intrahepatic
Referring to the liver lobulues
31
How to treat newborn's that have a different Rh blood type than their mother?
Mother is given Rhogam: purified antibody against Rh positive that binds Rh parts of fetal RBCs that passes the placenta and targets them for destruction so that maternal immune surveillance does not get involved
32
3 effects of portal HT?
1. Splenomegaly
2. Ascites
3. Portosystemic shunts
33
What is dyserythropoiesis?
The production of inappropriate RBCs in the bone marrow, which get destroyed
34
2 examples of prehepatic portal HT?
1. Emboli/thrombus in the portal circulation
| 2. Tumors in GIT putting pressure on the portal circulation
35
3 examples of intrahepatic portal HT?
1. Hepatitis
2. Cirrhosis
3. Cancer of the liver
36
Example of posthepatic portal HT?
Heart failure (especially right heart failure)
37
What are ascites? How do they form?
Accumulation of fluid in the peritoneal cavity
Decrease liver function leads to:
1. Portal hypertension => pooling of blood and lymph in liver sinusoids => increased hydrostatic pressure =>
2. Decreased albumin production => decreased oncotic pressure =>
3. Decreased aldosterone metabolism => increased Na and H2O kidney reabsorption => increased BP => increased hydrostatic pressure =>
=> increased transudation of fluid AND proteins from the plasma and space of Disse into peritoneal cavity
38
What type of portal HT causes ascites mainly?
Intrahepatic portal HT
39
What are the 6 portosystemic shunts and what do they lead to in portal HT?
1. Lower esophagus: esophageal branches of left gastric vein and azygos veins => esophageal varices
2. Upper anal canal: superior rectal vein and middle/inferior rectal veins => internal hemorrhoids
3. Umbilical: veins of the ligamentum teres and superor/inferior epigastric veins => caput medusa
4. Bare area of the liver: hepatic veins and inferior phrenic veins
5. Patent ductus venosus: left portal vein and IVC
6. Retroperitoneal: colonic veins and body wall veins
40
Why are esophageal varices dangerous?
High venous pressure inside the esophagus, so they can rupture, which can cause significant hemorrhaging => life threatening
41
What % of hepatic tissue is required for the liver to remain functional?
10%
42
5 effects of liver failure?
1. Hematologic disorders
2. Endocrine disorders
3. Skin disorders
4. Hepatorenal syndrome
5. Hepatic encephalopathy
43
What are 3 hematologic disorders caused by liver failure? Explain each.
1. Anemia due to lack of iron and fat-soluble vitamins necessary for the production of RBCs
2. Thrombocytopenia due to lack of iron and fat-soluble vitamins necessary for the production of RBCs
3. Coagulation defects due to lack of coagulation factors produced by the liver and vitamin K deficiency
44
What endocrine disorders are caused by liver failure? Explain each.
1. Decrease in sex hormone metabolism => disturbances in gonadal function:
- Women: menstrual irregularities (amenorrhea), loss of libido, and sterility
- Men: testicular atrophy, loss of libido, impotence, and gynocomastia
2. Decrease in aldosterone metabolism:
- Increase in salt and water retention
- Hypokalemia
45
What is thrombocytopenia?
Low platelet count
46
3 skin disorders caused by liver failure? Explain each.
1. Jaundice
2. Vascular spiders: incompetent valves in epidermal arteries and veins due to high estrogen levels causing dilation
3. Palmar erythema: red hot palms due to high levels of estrogen causing increased blood flow
47
Other name for vascular spiders?
Vascular nevi
48
In what other patients (other than liver failure) are vascular spiders and palmar erythema seen?
Patients with high estrogen levels:
1. Estrogen-secreting tumor
2. PCOS
3. Pregnancy
49
What is hepatorenal syndrome?
Renal failure seen during the terminal stages of liver failure that is characterized by:
1. Progressive azotemia
2. Increased serum creatinine levels
3. Oliguria
50
What is hepatorenal syndrome caused by? What is this called?
Caused by changes in blood flow to the kidney, not changes to the kidney itself = underfill theory
51
How can hepatorenal syndrome be reversed?
Liver transplant
52
What is oligouria?
Low urine output
53
What is hepatic encephalopathy? What is it caused by?
Totality of central nervous system manifestations of liver failure that range from lack of mental alertness to coma with possible memory loss and personality changes
Believed to be caused by an increase in ammonia => conversion to glutamine, which affects NT pathways in the CNS
54
How does the liver process ammonia? Where does it come from?
Ammonia from protein intake and bacterial overgrowth in the GIT (most ammonia), kidneys, and muscle metabolism enter the urea cycle in the liver to produce urea (to be excreted by the kidneys)
55
Serum measurements to test hepatocyte integrity?
Cytosolic hepatocellular enzymes:
1. Serum aspartate aminotransferase (AST)
2. Serum alanine aminotransferase (ALT)
3. Serum lactate dehydrogenase (LDH)
56
Serum measurements to test biliary excretory function?
Substances normally secreted in bile:
1. Serum bilirubin (total or direct aka conjugated only)
2. Urine bilirubin
3. Serum bile acids
Plasma membrane enzymes (to test damage to the bile canaliculus):
1. Serum alkaline phosphatase
2. Serum gamma-glutamyl transpeptidase (GGT)
57
Serum measurements to test hepatocyte synthetic function?
Proteins secreted into the blood:
1. Serum albumin
2. Coagulation factors: prothrombin (PT) and partial thromboplastin (PTT) times (fibrinogen, prothrombin, factos 5, 7, 9 and 10)
Hepatocyte metabolism:
1. Serum ammonia
2. Aminopyrine breath test (hepatic demethylation)
58
What is hepatitis? 5 causes? Most common cause?
Inflammation of the liver
Causes:
1. Reactions to drugs and toxins
2. Malaria
3. Infectious mononucleosis
4. Amebiasis
5. ***Hepatic virus
59
6 hepatic viruses?
A, B, C, D, E, G
60
What are the 2 mechanisms by which hepatic viruses cause liver injury? Describe each.
1. Direct cellular injury due to lysis of hepatocytes
| 2. Induction of immune responses against viral antigen causing the activation of stellate cells
61
What is the clinical course of viral hepatitis?
Asymptomatic infection => acute hepatitis => carrier state (with or without symptoms) => chronic hepatitis => fulminating disease with liver failure
62
What kind of virus is hepatitis A?
RNA virus
63
Transmission of hep A?
Fecal-oral transmission (food/water)
64
Incubation period for hep A?
4-6 week incubation between exposure and symptoms
65
2 risk factors for hep A?
1. Crowded, unsanitary conditions
| 2. Food and water contamination
66
What kind of virus is hepatitis B?
Double stranded DNA
67
What Igs created against hep A?
IgGs, only 1 type
68
2 symptoms of acute hepatitis infection?
1. Jaundice
| 2. Increase in ALT levels
69
Transmission of hep B?
1. Infected blood
2. Infected body fluids
3. Contaminated needles
4. Maternal transmission can occur if the mother is infected during the third trimester
70
Does hep A usually clear by itself?
YUP
71
Hep B prevention?
Hepatitis B vaccine prevents transmission/development (3 types of viral particles)
72
Incubation period for hep B?
4-6 months
73
How many antibodies are made in response to hep B infection?
3
74
Does hep B usually clear by itself?
NOPE
75
How can we tell if a patient will be able to clear a hep B infection by himself?
Acute response severity: the more severe the higher the chances of clearance
76
What hepatitis virus makes up most cases of post-transfusion hepatitis?
Hep C
77
What is hep C infection related to?
IV drug use
78
What % of hep C infections result in chronic liver disease?
50-80%
79
What does hep D virus depend on for replication?
Hep B virus
80
Describe the clinical course of the hep D virus.
Similar to hep A and B viruses
81
How is hep E transmitted?
Fecal-oral transmission
82
Where is hep E infection mainly seen?
Developing countries
83
To what virus is hep E clinically similar to?
Hep A
84
What hepatitis virus was recently discovered? How is it transmitted?
Hep G
Parentally and sexually transmitted
85
What is the chief reason for liver transplantation in adults?
Chronic viral hepatitis
86
What is chronic viral hepatitis caused by?
Caused by HBV, HCV, HDV
87
Treatment for chronic viral hepatitis?
No simple and effective treatment methods other than liver transplantation
88
What does hep D increase the risk of?
Liver cancer
89
What is liver cirrhosis?
Irreversible inflammatory disease that disrupts liver function and structure due to a decrease in hepatic function due to nodular regeneration and fibrotic tissue synthesis (fibrosis)
90
2 effects of liver cirrhosis?
1. Biliary channels become obstructed and cause portal hypertension
2. Blood can be shunted away from the liver and a hypoxic necrosis develops
91
Describe the development of liver cirrhosis.
SLOW
92
How do you classify liver cirrhosis?
Classified by the cause
93
What is the second most common reason for liver transplantation in adults?
Liver cirrhosis
94
Most common cause of liver cirrhosis? What else can cause it?
Alcohol
Hepatitis
95
What is alcohol? What is interesting about it?
Between a drug and a food: provides calories/energy BUT ir cannot be broken down or stored as a protein/fat/carb
96
Describe the mechanism of alcoholic liver disease.
Alcohol => metabolized into acetaldehyde =>
1. Acetaldehyde impedes mito electron transport system => H+ are shuttled out of mito => increased lipid synthesis + decreased mitochondrial oxidation of FAs => fatty liver/steatosis
2. Acetaldehyde impairs release of lipoproteins => fatty liver/steatosis
3. Acetaldehyde increases collagen synthesis + fibrinogenesis => liver fibrosis
97
List the 6 pancreatic enzymes. What secretes them?
1. Trypsin
2. Chymotrypsin
3. Carboxypolypeptidase
4. Ribonuclease
5. Pancreatic amylase
6. Lipases
Acinar cells
98
What is acute pancreatitis?
Escape of activated pancreatic enzymes into the pancreas and surrounding tissues causing auto-digestion
99
What organ makes more protein per cell than any other organ?
Pancreas
100
3 main causes of acute pancreatitis? How?
1. Gallstones
2. Alcohol
3. Pancreatic tumor
All activate trypsin within the acinar cells
101
4 symptoms of acute pancreatitis?
1. Pain
2. Nausea
3. Vomiting
4. Issues with deficiencies in pancreatic enzymes => digestion and absorption problems
102
How does the pancreas protect itself from the enzymes it produces?
1. Packages enzymes in zymogenic granules that contain anti-trypsin agents
2. Enzymes produced in inactive form and activated by acid and trypsin
103
Pathophysiology pathway of chronic pancreatitis due to alcohol?
Alcohol => increased basal pancreatic secretions + decreased trypsin inhibitor => auto-digestion
AND the excess pancreatic enzymes => protein plugs => duct obstruction => calcification
104
Clinical manifestation of chronic pancreatitis? Cause?
Usually manifests itself in episodes that are similar to those of acute pancreatitis with persistent recurring episodes of pain
Cause: often precipitated by alcohol abuse or overeating
105
Symptoms of chronic pancreatitis?
1. Anorexia
2. Nausea
3. Vomiting
4. Constipation
5. Flatulence
As the disease progresses:
6. DM
7. Malabsorption
106
What is contained in the gallbladder? 7 elements.
1. Bile salts
2. Cholesterol
3. Bilirubin
4. Lecithin
5. Fatty acids
6. Water
7. Electrolytes
107
What is cholelithiasis? Describe it.
Gallstones
Made of either crystallized cholesterol or bilirubinate
108
What 3 factors contribute to the formation of gallstones?
1. Abnormalities in the composition of bile
2. Stasis of bile
3. Inflammation of the gallbladder
109
Lab values for cholecystatis?
1. High serum bilirubin
2. High ALT
3. High alkaline phosphatase
110
Are gallstones more common in men or women?
Women
111
What GERD patients need an endoscopy?
1. Refractory to treatment
2. Chronic GERD
3. Bleeding or dysphagie
112
Signals that stimulate the gastric parietal cells to secrete acid? Which is the easiest to block?
1. Histamine*** => H2 receptor blocker
2. Para: ACh
3. Gastrin
113
What is a proton pump inhibitor? What is it used to treat?
Treatment against GERD
Blocks the H+ ATPase from secreting H+ in stomach lumen
114
Why are proton pump inhibitors a stronger treatment than H2 receptor blockers?
Cause if you use H2 blockers other signals could still cause acid secretion
115
Side effects of antacid GERD meds?
1. Indigestion
| 2. Increased infections
116
Between CD and UC which is more likely to have systemic manifestations?
UC
117
Which has cobble-stone appearance: CD or UC?
CD
118
Which spares the rectum: CD or UC?
CD
119
Which has friability of the mucosa: CD or UC?
UC
120
What vitamin deficiency is associated with steatorrhea?
ADEK (fat soluble vitamins)
