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341 Cards in this Set
- Front
- Back
What are prions? |
Infections proteins Prions are similar to normal proteins in the brain, but they fold differently Prions destroy the brain over time Ex. Mad Cow Disease |
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What are viruses? |
Obligate intracellular proteins that can make their own DNA, RNA, and proteins, but need a host cell in order to replicate |
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What are bacteria? |
Prokaryotes |
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What are fungi? |
Eukaryotic cells |
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What are protozoa? |
Single cell eukaryotes |
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What are helminth? |
Worms |
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What are ectoparasites? |
Lice is an example |
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What are the main portals of entry of antigens? |
Skin Respiratory GI GU |
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What does the skin produce to protect itself from foreign invaders? |
Antimicrobial fatty acids and defensins (small peptides that are toxic to bacteria) |
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What are most skin infections caused by? |
A break in the skin |
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What protects the GI tract from foreign organisms? |
Gastric acid Mucus Normal flora (good bacteria) Pancreatic enzymes (break down viruses with envelopes) |
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How can some organisms such as H. pylori survive in the stomach? |
They secrete things which raise the pH in the stomach |
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How are GI illnesses usually transmitted? |
Fecal oral |
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How is the respiratory tract protected from foreign organisms? |
Large particles can get stuck in the nasal mucosa If the large particle goes farther down the respiratory tract then cilia will move it up and it is either swallowed or coughed up Small particles can make it to the alveoli Macrophages in the alveoli can prevent the spread of infection |
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What happens when a virus enters the cell? |
Entry > uncoating > viral genome replication, mRNA synthesis > viral proteins Some viruses can transform cells into tumor cells (Ex. Epstein Barr virus) Some viruses prevent the cell from undergoing apoptosis (the virus can continue to hijack the cellular machinery and replicate |
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What is the difference between gram negative and gram positive bacteria? |
Gram positive bacteria have a more fluffy peptidoglycan layer Gram negative bacteria have LPS |
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How do bacteria and viruses hide from the immune system? |
Antigenic variation Capsules Down regulation of MHC class I Prevent fusion of lysosome and phagolysosome |
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What is antigenic variation? |
Some bacteria and viruses undergo antigenic variation Antigenic variation is when bacteria or viruses change their surface proteins (change cell surface to avoid antibodies) |
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What happens when an organism has a capsule? |
Capsules are slimy and antibodies have a hard time binding to them |
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What happens when a virus down regulates MHC class I? |
CD8 T cells do not know a cell is infected with a virus Ex. Herpes |
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What happens when an organism inhibits the fusion of the lysosome and the phagolysosome? |
Activation of enzymes to chew up organism does not occur The organism can escape in the cell and use cell machinery to continue to replicate and divide |
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What are some influenza like illnesses? |
Rhinovirus (common cold)- Usually no fever RSV- Can be nasty in pediatric population Adenovirus- URI that also causes pink eye Parainfluenza virus Bacterial influenza like illnesses |
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What could be seen on a lung biopsy of the case study patient with H1N1? |
Edema and inflammatory cells Hyaline membranes- Glassy homogenous appearance form proteins clumping together (bad sign) |
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What is influenza? |
Orthomyxoviridae family Enveloped virus containing 8 segemented ss (sense RNA) 3 types: A, B, C |
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Which type/s of flu are responsible for annual epidemics? |
A and B |
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Which type/s of flu are responsible for pandemics? |
A |
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Which type/s of flu infect humans? |
A and B |
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Which type/s of flu most commonly infect pigs? |
C |
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What determines the different types of flu? |
Antigenic differences in nucleoproteins and matrix proteins |
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How are viruses named? |
Classified on the basis of the 2 surface antigens- HA and N Type A, B, or C/Where first identified/# of isolates when first identified/Year isolated (Major type of HA, N) Ex. A/Sydney/5/85 (H1N1) |
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How many HA (Hemaglutinin) subtypes are there? How many have infected humans? |
16 5 (HA1, HA2, HA3, HA5, and HA9) |
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How many N (neuraminidase) subtypes are there? How many have infected humans? |
9 2 (N1, N2) |
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What is HA (hemagluttinin)? |
Located on virus surface
Binds to human cell surface and mediates binding and entry into the cell |
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What is N (Neuraminidase)? |
Located on virus surface When virus is ready to leave the cell N allows it to bud out of the cell |
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What is a M2 ion channel? |
Located on the virus surface Necessary for virus to uncoat itself when it's inside the human cell |
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What is the epidemiology of influenza? |
Causes annual epidemics and the occasional pandemic Epidemics generally occur in the Winter months in the U.S. New viruses are generated through 2 distinct changes: Antigenic drift and Antigenic shift |
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What is antigenic drift? |
Baby changes RNA polymerase is sloppy (doesn't go back and proofread) Mutations occur and change the virus HA receptor can change (antibodies don't bind as well) |
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Where do base changes from antigenic drift often occur? |
In the major antigenic variable regions Allows the virus to invade the immune system |
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How are annual epidemics prevented? |
There are more than 100 national influenza centers in more than 100 countries that conduct year-round surveillance for influenza viruses These labs will submit influenza viruses to 5 WHO centers (CDC Atlanta, London, Melbourne, Tokyo, Beijing) WHO makes the recommendation and each country decides how to design an implement the vaccine FDA does this in the U.S. |
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How is the influenza virus created? |
Grown in eggs For propagation of influenza virus, pathogen-free eggs are used 11-12 days after fertilization During the incubation period the virus replicates in the cells that make up the chorioallantoic membrane
Inject the virus into the egg and then isolate the virus from the egg The virus may then be chemically treated to strip off surface proteins to make the flu vaccines Whole process takes 7-8 months |
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What are the different types of flu vaccines? |
Trivalent inactivated Live attenuated Quadrivalent inactivated |
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What is the benefit of live attenuated vaccines? When are they contraindicated? |
Live attenuated replicates in cooler temperatures (in the nasal mucosa and not in the lungs where it's warmer) An IgG, IgA, and CD8 T cell response occurs (a more potent immune response) Contraindicated in asthma and immunosuppression (HIV) |
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What is a not so obvious benefit of vaccinating against flu? |
Protects against cardiovascular and cerebrovascular morbidity and mortality in patients with cardiovascular disease |
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What are some difference between flu and the common cold? |
Flu- Abrupt onset, Fever is common and lasts 3-4 days, Aches are common and severe, Chills are common, fatigue and weakness are common, sneezing, stuffy nose, and sore throat only occur sometimes, Chest discomfort and cough are common and can be severe, headache is common Cold- Gradual onset, fever is rare, aches are slight, chills are uncommon, fatigue only occurs sometimes, sneezing, stuffy nose, and sore throat are common, chest discomfort and cough are mild to moderate, a hacking cough may be present, headache is rare |
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How does Tamiflu work? |
Prevents the virus from budding outside of the human cell Shortens symptoms by a maximum of one full day Category C, but would give to a pregnant woman because flu can kill the fetus or cause other complications |
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What animals can influenza infect? |
Many different animals including ducks, chickens, pigs, whales, horses, and seals |
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What is antigenic shift? |
A major change in the genetic information of influenza virus |
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How does antigenic shift occur? |
Ex. Bird poops and pig sniffs it/eats it and human coughs on pigs This creates a mixing vessel for a new strain of influenza (genetic re-assortment occurs) The viruses enter a single cell together and a brand new virus is generated |
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What is a pandemic? |
A global disease outbreak An influenza pandemic occurs when a new influenza A virus emerges for which there is little or no immunity in the human population, begins to cause serious illness and then spreads easily from person to person worldwide Usually starts in china because flu season begins earlier there and there are a lot of farmers |
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What are the characteristics of a seasonal influenza epidemic? |
A public health problem each year Usually some immunity built up from previous exposures to the same subtype Infants and elderly most at risk |
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What are the characteristics of an influenza pandemic? |
Appear in the human population rarely and unpredictably Human population lacks any immunity All age groups, including healthy young adults |
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Where do "new" influenza viruses come from? |
Influenza A viruses are found in many animals including ducks, chickens, pigs, whales, horses, and seals All types of influenza viruses circulate in birds Pigs can be infected with avian and human viruses Often come from birds and pigs serve as the mixing vessel to create new strains |
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What influenza receptors do birds have? Humans? Pigs? |
Birds- a-2, 3 Humans- a-2,6 Pigs- Both |
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What was Spanish flu? |
Occurred in 1918 H1N1 20-40 million deaths |
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What was Asian flu? |
Occurred in 1957 H2N2 1-4 million deaths |
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What was Hong Kong flu? |
Occurred in 1968 H3N2 1-4 million deaths |
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How often do pandemics occur? |
3 or 4 times each century |
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When the Spanish flu occurred, the majority of deaths were in what age groups? What did many people die of? |
18-35 year olds Secondary bacterial infections |
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What was the Spanish flu? |
One of the greatest pandemics in the history of mankind Infected greater than 200 million people and 20-40 million were killed More died in a year than in the four year peak of the Black Plague in the 14th century People 15-34 years old were most affected (death rate 20 times higher than previous years) Approximately half of soldiers who dies in WWI died of flu Some evidence of strain first appeared in France in 1916 Infectious cDNA clones of complete 1918 strain recently finished- many similarities to current H5N1 avian flu Could this happen again? Vaccine/therapeutic availability and knowledge of epidemiology make another flu pandemic of the same proportions unlikely, but possible |
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What was H1N1 2009? |
An entirely new virus Genetic components came from flu viruses that infect pigs, birds, and humans The virus was easily transmitted among humans No one, except those who had been infected, or received vaccine is immune Despite its name, this strain of swine flu wasn't spread from direct contact with pigs or pork, but rather was transmitted among humans |
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What was the course of the H1N1 pandemic? |
April 17th- Cases found in California and Mexico April 26th- 2 countries, 38 cases May 1st- 13 countries, 367 cases May 9th- 29 countries, 3,440 cases May 27th- 48 countries, 13,398 cases October 24th- The president declared a national emergency |
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How was the H1N1 pandemic stopped? |
Because of patient education (hand washing and staying home if exhibiting symptoms) |
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What is measles? |
A leading cause of vaccine-preventable death and illness worldwide 20 million affected worldwide annually 350,000 deaths annually in developing countries Measles can harm the fetus during pregnancy (especially if before 12 weeks) Single stranded RNA virus of the paramyxovirus family 1 serotype (1 type of virus) |
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Why are children in developing countries more likely to die from measles? |
Poor nutrition in developing countries leads to a poor immune response |
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What complication do many people with measles die from? |
Pneumonia |
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How is measles transmitted? |
Respiratory droplets |
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How does measles cause cause infection? |
Droplets containing measles are breathed in > Measles goes to the alveoli where there are macrophages and dendritic cells > Measles binds to SLAM receptor on dendritic cell > Dendritic cell travels to local lymph node > along the way to the lymph node measles replicates and gets access the lymphatics/blood and spreads throughout the body causing viremia |
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What is the initial site of replication of measles? |
Macrophages/Dendritic cells |
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What are some complications of measles? |
Croup (infection of the larynx) Pneumonia (occurs commonly in developing countries) Diarrhea with protein-losing enteropathy (causes edema) Keratitis with scarring and blindness Encephalitis (acute inflammation of the brain) |
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How can measles affect the immune system? |
Measles can cause profound immunosuppression |
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What causes the measles rash? |
Hypersensitivity reaction mediated by T cells Cytokine production > Dilated skin vessels > leaky endothelium > edema T cells are at the site and surround the vasculature in the skin |
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When are Koplik's spots seen and what causes them? |
Typically occur a few days before the rash Thought to be caused by neutrophils coming to the site and causing ulcerations |
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What happens when measles infects the lung? |
Clumping of macrophages form a giant cell |
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What is mumps? |
Like measles, a member of the paramyxovirus family HA, NA surface proteins Replicate in lymphocytes (activated T cells) Spread through the blood, including salivary gland |
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How is mumps transmitted? |
Through respiratory droplets |
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How does mumps infect the salivary glands? |
Mumps likes to infect epithelial cells Different types of epithelial cells line the salivary glands Mumps infects and causes death of salivary epithelial cells by apoptosis or necrosis > Swelling/Edema |
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What causes the characteristic facial appearance of someone with mumps? |
Neutrophils and macrophages come to the site and release cytokines > Swelling in the interstitium of the glands > Clamping of the ducts > more swelling |
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What percent of patients with mumps have bilateral swelling? |
70% |
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What type of meningitis will 10% of patients with mumps end up with? |
Aseptic meningitis (meningitis caused by a virus) |
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What is mumps orchitis? |
Swelling of the testes Mumps can infect the testes and cause diffuse swelling which compromises blood flow and can lead to scarring and atrophy of the testicles Scarring and atrophy of the testicles can lead to sterility |
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What is a complication of mumps in women that is similar to mumps orchitis? |
Mumps infection of the ovaries |
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What is the MMR vaccine? |
Measles Mumps Rubella vaccine Live attenuated vaccine In the U.S., 2 doses are recommended for children First dose- 12 to 15 months old Second dose- Before entering school (4 to 6 years old) |
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Is the varicella vaccine long lived? |
It may not be long lived (need titer) Titer means you have IgG antibodies |
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Is varicella infection more dangerous in adults or children? |
Adults Varicella can be lethal in adults |
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What is Ebola? |
Discovered in 1976 Belongs to the Filoviridae family 5 types (4 cause disease in humans) Single stranded RNA |
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Where did the most current outbreak of Ebola originated? |
Guinea, Africa |
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How is Ebola transmitted? |
Infected animals to humans through close contact with body fluids (first case) Human to human (after first case) A bat may have started the first initial case |
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What are the symptoms of Ebola? |
Incubation period of 2-21 days Infectious Sudden fever, fatigue, myalgias, HA, sore throat Followed by vomiting, diarrhea, rash, acute renal failure, liver failure, hemorrhage |
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How does ebola kill patients? |
Ebola infects dendritic cells and tells them to go to sleep (cannot produce an immune response/activate T cells which are necessary to get rid of infection)
Ebola can also infect monocyte macrophages and cause them to produce TNF-a and IL-6 This causes a crazy systemic response called a cytokine storm (endothelial cells become leaky > fluid is redistributed to other parts of the body and this allows ebola to infect other cells types causing viremia) Patient goes into shock and bleeds out everywhere because of massive endothelial leakage (the RBC leak out) |
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What are the many consequences of Staphylococcal infection? |
Respiratory infection (usually a secondary infection) Osteomyelitis Skin infections (Some strains of staph produce lipases which break down lipids on the skin which can predispose to abscess) Endocarditis Food poisoning Toxic shock syndrome |
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What are some characteristics of staphylococcus? |
Staph typically colonizes on the skin Not all strains of staph produce toxins Some patients colonize staph in their nose Staph can produce a polysaccharide capsule which makes it slimy > Antibodies don't want to bind because it's not so tasty Staph can also bind to the Fc portion of the antibodies which prevents staph from being eaten |
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What are the symptoms of toxic shock syndrome? |
Hypotension Shock Multi-organ failure Rash |
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What causes toxic shock syndrome? |
Staph needs oxygen to grow (aerobic) The vaginal environment in mainly anaerobic Some tampons made in the 80's had a design which trapped oxygen Blood is nutrient rich Blood + oxygen from tampons = staph growth Staph produces toxins (superantigens) Staph can also produce an enzyme called cytolysin alpha-toxin which disrupts mucosal surfaces and allows toxins/staph to enter the blood stream |
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How do superantigens work? |
Superantigens hook up with APC and CD4 T cell This is a nonspecific interaction The superantigen binds to MHC Class II and TCR This interaction causes a massive immune response because many T cells are activated which leads to a cytokine storm and shock |
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What can happen if potato salad is left out for a long time and then eaten? |
Staph can colonize and release toxins Gastric juices don't destroy the toxins N/V can occur 2-8 hours after eating Symptoms usually resolve within 24-48 hours |
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What should antibiotic use, watery diarrhea, and living in a nursing home make you suspicious of? |
C. diff |
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What is Giardia lamblia/intestinalis? |
Flagellated protozoans Most common pathogenic parasitic infection in humans Spread through fecally contaminated water (Ex. Swimming in contaminated water and swallow some) Resistant to chlorine If pools are not filtered often G. lamblia can grow and cause infection |
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What are important for clearance of G. lamblia/intestinalis? |
IgA and IL-6 |
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How do G. lamblia/intestinalis survive in the stomach? |
They survive in cysts |
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How do G. lamblia/intestinalis cause infection? |
Infect small intestinal cells and destroy the brush border causing malabsorption and diarrhea |
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How do G. lamblia/intestinalis avoid the immune response and survive? |
They can change their flagella (surface proteins) which allows them to avoid immune response They can survive for months |
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What is salmonella? |
Gram negative bacilli Two types- Non-typhoid and typhoid (causes systemic issues) Non-typhoid S. enteritidis 1 million cases per year Summer & Fall Contaminated food Chicken |
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How does antigen sampling in the intestines via M cells work? |
M cells are lined throughout the intestines and bring in antigens (sampling) Macrophages exist under the M cells and are there to eat things Macrophages go to the Peyer's patches (lymph nodes in the gut) |
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How does salmonella/shigella invade the intestines? |
Salmonella/Shigella have evolved ways to trick the cell to ingest it Zipper mechanism- Bind to cell receptors > Trigger cytoskeleton rearrangement to allow engulfment of organism (endocytosis) Trigger mechanism- Organism can trigger its way in to the cell with no receptor by injecting a hollow needle into the cell and injecting its own proteins into the cell > Hijacks the cytoskeleton > The organism tricks the cell to rearrange the cytoskeleton and engulf the organism Some organisms have evolved ways to escape the endosome and cause infection |
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What is a type 3 secretion system? |
A type of secretion system for invading the cell Organisms don't have receptors to invade the cell and will instead inject hollow needle into the cell |
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Which part of the gut does salmonella like to colonize? |
The ileum Bacteria sense the environment of the gut (osmolarity, oxygen levels, etc.) In the terminal ileum there is acetate and formate which salmonella like (allows salmonella to illicit a type 3 secretion system and invade) |
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What is shigella? |
Initially isolated during the Japanese red diarrhea epidemic of 1897 Gram negative bacilli 4 major strains Unencapsulated, non-motile, facultative anaerobe (can live with or without oxygen) One of the most common causes of "bloody diarrhea" 165 million cases worldwide |
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Which part of the gut does Shigella like to colonize? |
Colon (left side) |
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What else may also cause left sided abdominal pain? |
Diverticulitis may cause LLQ pain in caucasians May cause right sided pain in asians |
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How does shigella cause infection? |
M cells sample antigens (shigella) > Shigella enters the M cell and a macrophage eats it > Shigella escapes the phagosome (no phagolysosome fusion) > Shigella binds to receptor on enterocyte and is taken up into cell (comes in as phagosome) > Shigella escapes the phagosome and hijacks the cytoskeleton of the cell (actin and microtubules) and uses it as a ladder to move throughout the cell > Shigella moves across the cell and infects adjacent cell > Shigella exits out into the GI lumen and causes infection |
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What are the symptoms of a shigella infection? |
Fever, abdominal pain, bloody diarrhea Acute colitis Self-limiting usually, but can last as long as a month |
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What is Campylobacter jejuni? |
Most common bacterial enteric pathogen in developed countries Comma-shaped, flagellated, gram - Chicken, unpasteurized milk, contaminated water Causes traveler's diarrhea Patho is poorly understood 4 virulence factors- Motility, adherence, toxin production, and invastion |
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What environmental reservoirs can lead to human infection by C. jejuni? |
Chicken, unpasteurized milk, and contaminated water C. jejuni colonizes the GI tract of the chicken > The chicken poops and contaminates water > Human drinks the water and can get infected A cow can drink the contaminated water > Unpasteurized milk can infect humans C. jejuni can infect humans via uncooked chicken |
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How does C. jejuni survive in water? |
It forms a biofilm on water which protects the organism so it can continue to replicate |
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How does C. jejuni cause infection? |
C. jejuni circumvents the mucus layer in humans and interacts with the intestinal epithelial cells causing IL-8 production C. jejuni enters the enterocyte > The enterocyte becomes angry and produces IL-8 which acts as both a cytokine and chemokine > In the subepithelium macrophages, dendritic cells, and neutrophils will influx and produce pro-inflammatory cytokines > T helper 1 specific immune response occurs > Inflammation > Clearance NF-KB is a transcription factor (activates genes) which is important in activating genes responsible for an inflammatory cytokine response |
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What are some complications of an infection with C. jejuni? |
Reactive arthritis (patients with the HLA-B27 gene are especially predisposed) Linked to Guillain-Barre syndrome |
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Is C. jejuni a self-limiting infection? |
Yes |
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What are the 3 types of E. coli we learned about in class? |
Enterotoxigenic E. coli Enterohemorrhagic E. coli Enteroinvasive E. coli |
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Which strain of E. coli secretes 2 different types of toxins which cause watery diarrhea? |
Enterotoxigenic E. coli |
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How is enterotoxigenic E. coli (ETEC) transmitted? |
Contaminated meat and many other ways |
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How does Enterotoxigenic E. coli cause watery diarrhea? |
Via Heat-Labile toxin and Heat-Stable toxin HL toxin has an A and B subunit HL toxin binds to a receptor on the cell and is taken in as a phagosome/vesicle > HL has retrograde transportation into the golgi (goes to the golgi first rather than the ER) > Subunit A activates adenylyl cyclase > Activates cAMP (2nd messenger) > Protein kinase A gets activated > Increase activation of this pathway causes excretion of Cl into the gut via CFTR > Na and H20 are also excreted into the gut causing watery diarrhea) HS toxin activates guanylyl cyclase and also leads to cAMP and protein kinase A activation > Watery diarrhea via same mechanism |
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How did one strain of enterohemorrhagic E. coli (EHEC) infect many children? |
Caused abdominal pain, diarrhea, and death The source of the infection was apple juice from school The apple juice was made from apples from an apple farm that would fall off the tree into deer poop The E. coli from the deer poop got onto the apples and into the apple juice The apple juice was not sufficiently pasteurized to kill any pathogens it contained |
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What is the infection source of EHEC? |
Cattle and other ruminants are the main E. coli carriers Humans can get E. coli from uncooked meat and raw milk and fruits and vegetables |
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What is the incubation period for EHEC? |
3 to 8 days |
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What are the symptoms of EHEC? |
Stomach muscle spasms, diarrhea (sometimes bloody), fever, and vomiting Complications- Hemolytic Uremic Syndrome (HUS) Death rate- 3-5% |
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How does EHEC cause infection? |
EHEC produces shiga toxin EHEC enters the cell and gets access to circulation > Shiga toxin binds to receptor on endothelial cell > Shiga toxin is brought into the endothelial cell via a vesicle and is shuffled into the ER > Shiga toxin disrupts protein synthesis > Endothelial cells start to die > Platelet aggregation > Fibrin contributes to microthrombis forming in circulation > RBC that get stuck fragment and release hemoglobin > Fragments and hemoglobin wind up in kidney > Clog the kidney and cause acute renal failure Infection leads to diarrhea and hypovolemia (dehydration) which can also cause acute renal failure Acute renal failure can cause death |
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What is enteroinvasive E. coli (EIEC) |
Similar to shigella Does not produce toxins Transmitted by food, water, or person to person |
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Should neutrophils or lymphocytes be present in the stool? |
No Neutrophils indicate bacterial infection Lymphocytes indicate viral infection |
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What part of the gut does C. diff infect? |
The large intestine |
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What would you seen on the colonoscopy of someone with C. diff? |
Hyperemic colon walls and psudomembranes |
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What is C. diff most commonly associated with? |
Antibiotic use (specifically clindamycin) C. diff normally lives in the gut > Antibiotics decrease good bacteria > C. diff proliferates |
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What is the treatment for C. diff? |
Oral vancomycin |
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How does C. diff cause infection? |
C. diff colonizes on the mucosal surface and releases enzymes like proteases which allow it access to the epithelium > C. diff releases toxins A and B which are taken inside the cell and kill the cell via apoptosis and necrosis > Dead epithelium slough off and form pseudomembranes which consist of dead cells, neutrophils, and macrophages |
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What is C. diff? |
Gram +, motile bacteria Associated with advanced age, hospitalization and antibiotic treatment 30% of hospitalized patients are colonized with C. diff |
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What are the symptoms of C. diff? |
Fever, leukocytosis, abdominal pain, cramps, and hypoalbuminemia |
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What cases hypoalbuminemia in patients with C. diff? |
Epithelial cell death creates holes in the gut which allows albumin to leak into the gut Albumin that is leaked into the gut is pooped out |
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What are good questions to ask to screen a patient for C. diff? |
How many times are you going a day? (15-20 times) What does it smell like? (like death) What does it look like? (watery) |
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What do bacteria in the GI do? |
There are trillions of bacteria in the ileum and colon Bacteria colonize and protect against pathogens Facilitate digestion, help with absorption of Vitamin K and folate, and shape development of intestinal epithelial cells |
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What is the function of each part of the GI tract? |
Mouth- Chew food, saliva (adds water and digests carbohydrates Esophagus- Swallows Stomach- Mix and dilutes chyme, gastric secretions (digest protein, add intrinsic factor, acidic) Small intestine- Bile emulsifies fat, Pancreatic secretions, Intestinal secretions (digest fat, protein, and carbohydrate), absorption of nutrients Colon- Absorbs water and electrolytes Rectum- Storage until defecation |
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What is the role of amylase? |
Released by salivary glands and the pancreas Breaks down carbs |
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What does distention of the antrum of the stomach cause to happen? |
Distention > Release of gastrin > Gastrin produced by G cells stimulates production of acid in the stomach |
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What are the layers that exist in the GI tract from the esophagus to the rectum? |
Inner layer- Mucosa (Epithelium, lamina propria, muscularis mucosa) Middle layer- Submucosa Outer layer- Muscularis externa (longitudinal and circular muscle) Outer serosa- Serous membrane consisting of mesothelium (also known as visceral peritoneum) |
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What is the function of the mucosa? |
Production of mucus (protective coat), secretion of digestive enzymes to break down food, absorption of breakdown products |
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What does the submucosa contain? |
Lymphatics, blood vessels, connective tissue, nerves |
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What is the role of lymphatics and vascular channels in the submucosa? |
Pick up absorbed nutrients and carry them back to the liver for processing |
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What is the role of the muscularis externa? |
Responsible for peristalsis |
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What type of epithelial cells does the esophagus contain? |
Stratified squamous epithelium |
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What are basal cells and where are they located? |
Located near the basement membrane which provides nutrients to basal cells Basal cells are like stem cells (they divide and form many layers) |
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Why must the esophageal squamous epithelium be lubricated? |
To protect from acid |
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What kind of cells are gastric pits lined with? |
Parietal cells (secrete HCl) Chief cells (secrete pepsinogen) Endocrine cells (G cells) produce gastrin which tickles other cells in the stomach to produce HCl |
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How is pepsin created? |
Pepsinogen + HCl = Pepsin (degrades proteins) |
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What type of cells is the antrum (bottom) of the stomach lined with? |
Mucus (foveolar) cells Secrete mucus to protect the stomach from acid |
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If a patient presents with heartburn, regurgitation, and epigastric pain, what is one thing that should be on your differential that is not GI related? |
MI |
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What should you initially treat GERD with? |
PPI |
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What is the purpose of the lamina propria? |
Provides support and nutrition to the epithelium Contains many different cells including fibroblasts, plasma cells, macrophages, etc. |
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What is hyperplasia? |
Increasing cell number |
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How would a biopsy of reflux esophagitis look? |
Basal cell hyperplasia extending 20% into the epithelium (15% or less is normal) and papillae elongation Hyperplasia occurs to accommodate damage from acid Papillae elongate to provide more nourishment to the epithelium |
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What cells are recruited to the site in reflux esophagitis? |
Eosinophils recruited first followed by neutrophils The more neutrophils coming to the site correlates with more extensive disease |
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What is reflux esophagitis? |
Reflux of acid from the stomach due to reduced LES tone Reflux of gastric juices is central to the development of mucosal injury Sometimes bile from the duodenum can exacerbate damage ETOH, smoking, obesity, and pregnancy can exacerbate symptoms In many cases the cause is unknown |
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What does metaplastic (cell type change) columnar epithelium containing intestinal goblet cells in the distal esophagus suggest? |
Barrett's esophagus |
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What is Barrett's Esophagus? |
Chronic GERD Metaplasia of the lower esophageal mucosa from stratified squamous epithelium to nonciliated columnar epithelium with goblet cells Common in 50-60 year old white males Increased risk of esophageal adenocarcinoma |
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If a GI series (radiographs) reveals narrowing of the esophagus, what should you suspect? |
Cancer |
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What is dysplasia? |
Neoplastic epithelium that remains confined to the basement membrane (has not invaded other structures) Precancerous |
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What does biopsy of esophageal dysplasia look like? |
Epithelial cells enlarged with enlarged hyperchromatic (nucleus is more dense- more chromatin from uncontrolled cell division) nuclei |
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What does dysplasia cause? |
Loss of cell polarity (loss of organization) Ex. HCl should be secreted into the lumen of the stomach, but instead it would go to the other side of the cell |
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What are the two types of esophageal carcinoma? |
Adenocarcinoma Squamous cell carcinoma |
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What does ulceration of the esophagus suggest? |
Cancer (adenocarcinoma) |
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What is adenocarcinoma? |
Malignant proliferation of glands Usually occurs in the distal 3rd of the esophagus (Barrett's) Can invade adjacent gastric cardia Tell your patients to eat fruits and veggies Some strains of H. pylori decrease risk (cause gastric atrophy > decreased acid production > less acid to damage esophagus) Most common in white males Most common type of malignancy in the west |
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What are back to back glands, and what are they indicative of? |
Glands in the esophagus enlarge (back to back glands) to try to protect the esophagus from acid Indicative of high grade dysplasia (think cancer) |
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Where does invasive esophageal carcinoma invade? |
Beyond the basement membrane |
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What are some causes of esophageal cancer? |
Mutation of p53 early on (P53 is a tumor suppressor; if you can't suppress cell division you get cancer) Amplification of c-ERB-B2, cyclin D1 and cyclin genes Allelic loss of p16/INK4a Increase expression of TNF alpha, NF-kB Spread by mucosal lymphatic vessels |
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How can a mutation of p53 cause cancer? |
P53 is a tumor suppressor If you can't suppress cell division, you get cancer |
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How can amplification of ERB-B2 cause cancer? |
C-ERB-B2 is an oncogene (gene that can transform a cell into a tumor cell) Amplification of ERB-B2 leads to cancer |
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How can amplification of cyclin D1 and cyclin genes cause cancer? |
Cyclin D1 and cyclin genes regulate the cell cycle Amplification can lead to progression through the cell cycle without sufficient checking which can lead to cancer |
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How can allelic loss of p16/INK4a cause cancer? |
Loss of p16/INK4a (cyclin dependent kinase inhibitor) leads to uncontrolled cellular proliferation and can cause cancer |
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How can increased expression of TNF-a cause cancer? |
TNF-a causes inflammation Unchecked inflammation can cause cancer |
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How can increased expression of NF-kB cause cancer? |
NF-kB is a transcription factor If NF-kB is activated all the time it goes and activates genes which can cause cause of expression of TNF-a This can cause cancer |
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What is squamous cell carcinoma? |
Malignant proliferation of squamous cells Most common esophageal cancer worldwide Arises in the upper or middle third of the esophagus |
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What are symptoms of esophageal cancer? |
Late detection = poor prognosis Progressive dysphagia (solids to liquids) Weight loss Hematemesis Hoarse voice (because of recurrent laryngeal nerve involvement) |
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What lymph nodes are affected from cancer of the upper 1/3 of the esophagus? Middle 1/3? Lower 1/3? |
Upper 1/3- Cervical nodes Middle 1/3- Mediastinal or tracheobronchial nodes Lower 1/3- Celiac and gastric nodes |
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How many liters of food can the stomach hold? |
1-1.5 L |
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What is pale conjunctiva indicative of? |
Anemia |
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What is black stool indicative of? |
Upper GI bleed |
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If a 65 year old male comes in with fatigue and is anemic, what should be at the top of your differential? |
Colon cancer |
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Why may hemoglobin be low? |
From bleeding |
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Why may albumin be low? |
Chronic alcohol abuse causing cirrhosis |
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What can cause coffee-ground gastric contents? |
From bleeding in the stomach Stomach acid oxidizes hemoglobin into brown hematin (coffee ground appearance) |
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What are 75% of gastric ulcers caused by? |
H. pylori |
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Where does H. pylori like to live? |
The antrum of the stomach |
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What will be seen on a stomach biopsy of someone with H. pylori? |
Neutrophils Swelling/edema (no gastric pits) T cells and B cells may be present in chronic infection |
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What is acute gastritis? |
Acidic damage to the stomach mucosa Transient mucosal inflammatory process (as long as you take away the cause- H.pylori or NSAIDs) pH of the stomach is close to1 Protective mechanisms are disturbed |
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The entire gastric epithelium is replaced how often? Why is this important? |
Replaced every 2-6 days Chemotherapy suppresses mitosis (could cause acute gastritis) |
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What are some risk factors for acute gastritis? |
NSAIDs ETOH (damages the mucosa) Severe burns |
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How can severe burns cause acute gastritis? |
Severe burns can cause a curling ulcer Patients with severe burns are in a state of hypovolemia The stomach has a rich vascular supply which takes away acid Hypovolemia = decreased blood supply > stomach can't sweep away acid |
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How do NSAIDs cause gastritis and ulcers? |
Prostaglandins lead to decreased acid and mucus production Prostaglandins also stimulate bicarbonate secretions which neutralize acid NSAIDs inhibit prostaglandins |
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What are some other things that may cause acute gastritis? |
Intracranial injury Systemic acidosis Hypoxia Shock |
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How can intracranial injury cause acute gastritis? |
Swelling in the brain (intracranial injury) leads to stimulation of vagal nuclei in the brain > Increases HCl Vagal cells release Ach which binds to receptors on epithelial cells and stimulates HCl production |
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How can systemic acidosis cause acute gastritis? |
Systemic acidosis causes low pH inside the cells which can lead to acute gastritis |
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How can shock cause acute gastritis? |
Decreased blood flow interferes with the removal of acid from the lamina propria which can lead to gastritis |
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What would you do to prevent patients with intracranial injury, systemic acidosis, hypoxia, or shock from developing acute gastritis? |
PPI ulcer prophylaxis |
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How is gastric acid (HCl) formed in the stomach? |
Histamine, gastrin, and Ach all bind to receptors on the basolateral membrane of the parietal cell The parietal cell brings in chloride A proton pump (ATPase pump) pumps K into the cell in exchange for H > This leads to the opening of a Cl channel > H and Cl join to form HCl |
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How do H2 blockers lower HCl production? |
They prevent histamine from binding to its receptor on the parietal cell which lowers HCl production |
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How does swelling in the brain cause an increase in HCl production? |
Swelling in the brain causes the vagal nuclei in the brain to tickled > Ach is produced > Increased HCl production |
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What occurs initially as a result of acid damage? And after that? And after that? |
Superficial inflammation > Erosion (loss of superficial epithelium) > Ulcer (loss of mucosal layer) |
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What are the two types of chronic gastritis? |
H. pylori Chronic autoimmune gastritis |
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What occurs in chronic autoimmune gastritis? |
Destruction of parietal cells because antibodies attack parietal cells and/or there are antibodies directed against intrinsic factor (needed to absorb B12) Pathogenesis mediated by T cells (hypersensitivity type IV) Parietal cells being attacked causes atrophy of the mucosa and persistent inflammation Achlorhydria (low HCl production) is associated with autoimmune gastritis G cells respond by producing more gastrin to compensate for low HCl > This causes G cell hyperplasia Antibodies against intrinsic factor cause anemia (megaloblastic) |
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What is H. pylori? |
Spiral-shaped bacilli Present in 90% of individuals with chronic gastritis (antrum) Mode of transmission of understood Humans are the only host Intraepithelial neutrophils and plasma cells (Acute- neutrophils; Chronic- Neutrophils and plasma cells) |
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Compare and contrast duodenal ulcers and gastric ulcers |
Duodenal ulcers are mostly caused by H. pylori Gastric ulcers cause more pain on eating Duodenal ulcers are associated with pain relief from eating (The duodenum prepares for acid coming from the stomach and releases things to neutralize acid like bicarbonate and secretin) Duodenal ulcers almost never lead to malignancy Gastric ulcers can lead to malignancy |
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What are some H. pylori virulence factors? |
Flagella Adhesin proteins (attachment to epithelial cells) Urease (produces ammonia which neutralizes acid because H. pylori likes a higher pH) LPS (induces an inflammatory response) VacA (formation of vacuoles which leads to apoptosis, disruption of epithelial junctions, blockage of T cell response) CagA (alteration of signaling pathways, cytoesquelet rearrangement, alteration of tight junctions) |
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What is the pathogenesis of H. pylori infection? |
Production of urease neutralizes gastric acid Mucosal damage occurs by mucinase which chews through the mucosa > Leads to inflammation and mucosal death Ammonia also contributes to mucosal cell death An increase in IL-6 and IL-8 occur IL-6 is inflammatory and IL-8 leads to recruitment of neutrophils to the site which further exacerbates inflammation |
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What is MALT lymphoma? |
A type of lymphoma that is caused by chronic H. pylori infection B cells like to live in the germinal center of lymphoid tissue Persistent H. pylori leads to B cell lymphoma One of the few cancers that can be resolved just by removing the cause (H. pylori) |
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Why would a patient with celiac disease have hypoproteinemia and hypoalbuminemia? |
Because of malabsorption of the building blocks needed to make protein |
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Why would a patient with celiac disease be anemic? |
Because iron is not being absorbed |
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If serum tests for IgA antiendomysial and anti-IgA tissue transglutaminase (IgA-tTG) antibodies are positive, what does this indicate? |
Celiac disease |
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What is endomysial? |
A connective tissue that wraps around each muscle fiber |
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Does IgA antiendomysial cause mylagia? |
No, because IgA is only present in mucus |
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Describe the structure of the small intestinal wall |
Villi Epithelial and goblet cells line the villi Capillary network in each villus Intestinal glands |
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What kind of cells does the lamina propria contain? |
Fibroblasts and immune cells |
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Describe the structure of the large intestine |
No villi Columnar epithelium More goblet cells than the small intestine |
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What are small intestinal epithelium called? |
Enterocytes |
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How often are enterocytes shed? |
Every 3-5 days |
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What are brush border enzymes? |
Enterocytes express enzymes on their surface called brush border enzymes Brush border enzymes further help break down products within the intestine |
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What is a crypt of Lieberkuhn? |
Where small intestinal stem cells are located Responsible for regeneration of cells |
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What is a lacteal? |
Lymphatics located in the villi Absorb fat in the small intestine |
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How does lactose intolerance cause diarrhea? |
Lactose intolerance occurs when there is no lactase (brush border enzyme) to break down lactose into glucose and galactose (monosaccharides) The small intestine can only absorb monosaccharides (not disaccharides) Disaccharides that are not broken down draw water into the lumen (sugar is osmotically active like salt) causing diarrhea |
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How are glucose and galactose brought into the enterocyte? |
Large carbohydrates are broken down to disaccharides > disaccharides are broken down by brush border enzymes into monosaccharides SGLT-1 transporter is a sodium glucose cotransporter the lines the lumen surface In order to bring glucose and galactose into the cell, the enterocyte creates a sodium gradient (the enterocyte allows sodium to come into the cell) > higher levels of sodium in the enterocyte allows glucose and galactose to come into the cell (no energy required) |
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How are glucose and galactose exported out of the enterocyte? |
Exporting glucose and galactose out of the enterocyte ATP is needed Sodium goes out of the cell and potassium comes into the cell Glucose and galactose leave the cell via the GLUT-2 transporter (glucose cotransporter) |
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How is fructose brought into the enterocyte and exported? |
By passive/facilitated diffusion |
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What happens to glucose, galactose, and fructose after they are exported from the enterocyte? |
They are taken to the liver This is how we get our nutrients from the small intestine |
|
How is dietary fat absorbed? |
Stomach agitation (stomach acid starts to break things down) Bile salts synthesized in the liver are excreted into the duodenum along with pancreatic lipase (likes to chew up fat) Lipase chews up triglycerides into monoglyceride and free fatty acids Bile salts form micelles which collect monoglycerides and free fatty acids > Mixed micelle is formed The enterocyte will take the mixed micelle inside and break it down into triglycerides > forms water soluble triglycerides (must be water soluble in order to travel back to the liver) Chlyomicrons (water soluble triglycerides) will go to the lymphatics and to the liver where they will be further processed |
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How many intraepithelial lymphocytes should you see in a villus? |
Occasional intraepithelial lymphocytes You do not want to see too many |
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Flattened duodenum from celiac disease causes what? |
Decreased absorption |
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What begin to accumulate in celiac disease? |
Intraepithelial lymphocytes (CD8+ T cells) |
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What is celiac disease? |
Immune-mediated enteropathy triggered More common in women and people 30-60 years old Chronic diarrhea, anemia, bloating T cell-mediated autoimmune disease Results in villus shortening, crypt hyperplasia, and lymphocytic infiltration of the epithelium Loss of immune tolerance (immune system attacks self) |
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Describe the pathophysiology of celiac disease |
Gluten is rich in proline and glutamine which protects is from being degraded by stomach acid Brush border enzymes cleave gluten into peptides called gliadin > gliadin peptide comes through the epithelial cells > tTH deaminates the gliadin (removes amide group) and targets the peptide for degradation > Gliadin is a highly negatively charged peptide and HLA molecules (DQ2 or DQ8) like negatively charged peptides > Gliadin has a higher affinity for HLA molecule than peptide already sitting in HLA molecule, so Gliadin displaces peptide > Autoreacitve T cell (reactive to gliadin) gets out of the thymus and sees the gliadin in the HLA and releases IFNy > Causes epithelial cells to upregulate MIC-A (like a MHC class I molecule) > Autoreactive T cell (T helper cell) will tickle a B cell which will produce antibodies (Anti-gliadin, Anti-endomysium, and Anti-tTG Gliadin can also bind to enterocytes and make them angry cause them to produce IL-15 which tickles CD8+ intraepithelial lymphocytes causing them to become activated Because there is an increased expression of MIC-A, the CD8+ T cell will go and kill the enterocytes which leads to a loss of villi |
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What is IBD? |
Idiopathic Chronic
More common in females in their teens and early 20's Hygiene hypothesis (we are too clean) SNPs |
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What factors can lead to the development of IBD? |
Genetic predisposition (Certain genes have been linked to these disease)
Gut microbiota Host immune response (innate/adaptive) |
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What is the distribution like in ulcerative colitis? |
Starts in the rectum and moves up No skipped lesions Confined to the large intestine Pseudopolyps and ulcers in the mucosa and sometimes the submucosa |
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What type of pain do patient's with UC complain of? |
LLQ pain (location of rectum) |
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What is the distribution of Crohn's disease like? |
Skipped lesions Lesions can be found anywhere from the mouth to the anus Transmural inflammation (all layers affected) Ulcerations and fissures can form |
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Which IBD is associated with bloody diarrhea? |
Ulcerative colitis |
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What is the hallmark of ulcerative colitis? |
Crypt abscess Crypts are full of neutrophils Crypts may also be seen in Crohn's disease, but are not nearly as prevalent |
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What can ulcerative colitis lead to? |
Cancer |
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What is protective against UC? |
Smoking |
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The lead pipe appearance of the large intestine from UC is caused by what? |
Loss of haustra due to diffuse inflammation |
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What is seen on the biopsies of 40% of patient's with Crohn's disease? |
Granulomas Granulomas contain lymphocytes |
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What is Crohn's disease? |
Recurrent, granulomatous type of inflammatory response that can affect any area of the GI tract Terminal ileum or cecum is the most common portion of the bowel where inflammation occurs |
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What type of inflammation is present in Crohn's disease? |
Transmural chronic inflammation |
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Where may some Crohn's disease patients experience pain/tenderness? |
RLQ pain because that is where the ileum is |
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What type of fissure can Crohn's patients sometimes get? |
Knife-like fissures (like a stab wound in the ileum) |
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What can knife-like fissure cause? |
Damage to all the layers can damage stem cells Knocking out the stem cells does not allow the tissue to restore to normal Can cause granulation and fibrosis Myofibroblasts are part of the healing process |
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What is cobblestoning? |
Seen in Crohn's disease Is a result of the gut trying to heal |
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What causes creeping fat in people with Crohn's disease? |
Fat surrounds the intestines Myofibroblasts contract the wound The intestines contract and the fat is pulled closer to the intestine (creeping fat) This is a part of the healing process when stem cells are knocked out |
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Describe the pathophysiology of Crohn's disease |
TH1 and TH17 (autoreactive) are predominant in Crohn's disease and mediate inflammation T17 recruits neutrophils and causes inflammation TH1 cells produce IFNy which makes macrophages angry causing them to secrete TNF-a |
|
How may some Crohn's disease patients be treated? |
Treated with biologic agents like TNF-a antibodies Alleviates symptoms Patients must be tested for Tb every 6 months because TNF-a protects against Tb |
|
Describe the pathophysiology of UC |
TH2 (autoreactive) are predominant in UC Patients with UC have elevated levels of IL-13 in their serum |
|
What do islet cells (endocrine) in the pancreas produce? Acinar (exocrine) cells? |
Insulin Digestive enzymes |
|
What do acinar cells contain? |
Zymogen granules which contain inactive digestive enzymes |
|
What is acute pancreatitis? |
Inflammation and hemorrhage of the pancreas that results in autodigestion of the tissue (from enzymes, mainly trypsin) May be acute or chronic (acute form is considered a medical emergency) The pancreas lacks a fibrous capsule so destruction may progress into tissue surrounding the pancreas and substances released by necrotic tissue lead to widespread inflammation (hypovolemia and circulatory collapse may follow) |
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What are some causes of acute pancreatitis |
Trauma (Ex. MVA) Hypercalcemia (Calcium activates enzymes, so if you have a lot of calcium you can activate enzymes and cause pancreatitis) Hyperlipidemia Scorpion stings Mumps Coxsackie B virus Rupture of posterior duodenal ulcer (pancreas is right behind the duodenum) |
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What are the symptoms of acute pancreatitis? |
Abdominal pain (cardinal symptom) Anorexia N/V Edema (If the pancreas is unable to release enzymes then you get malabsorption > low albumin > edema) 10% can develop psudocysts |
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What ethnic group are more predisposed to pancreatitis? |
Native Americans |
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What are three pathways in the pathogenesis of acute pancreatitis? |
Duct obstruction Acinar cell injury Defective Intracellular transport |
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How does duct obstruction lead to acute pancreatitis? |
Cholelithiasis (ampullary obstruction) and Chronic alcoholism (ductal concretions) > Duct obstruction blocks enzymes from reaching the duodenum > edema and inflammation > impaired blood flow > ischemia > Acinar cell injury/death > activated enzymes > acute pancreatitis |
|
How does acinar cell injury lead to acute pancreatitis? |
Alcohol, Drugs, Trauma, Ischemia > Release of intracellular proenzymes and lysosomal hydrolases > activation of enzymes (intra or extracellular) > acinar cell injury/death > activated enzymes > acute pancreatitis |
|
How does defective intracellular transport lead to acute pancreatitis? |
Alcohol and duct obstruction > Delivery of proenzymes to lysosomal compartment > intracellular activation of enzymes > acinar cell injury/death > activated enzymes > acute pancreatitis |
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What are the different pancreatic enzymes, and what can they cause? |
Proteases (proteolysis)
Lipase and phospholipase (fat necrosis) Elastase (hemorrhage from damage to elastic fibers of blood vessels) |
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What are the mediators in acute pancreatitis? |
Inflammation Vascular injury Acinar cell injury Activation of proteolytic enzymes (trypsin) Activation of clotting cascade (can lead to DIC) |
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What does acute pancreatitis eventually result in? |
Resolution |
|
What are the mediators in chronic pancreatitis? |
ETOH oxidative stress Inflammation |
|
What does chronic pancreatitis result in? |
Pancreatic fibrosis and acinar cell loss |
|
Do people with pancreatitis develop diabetes? |
Not usually Pancreatitis affects the exocrine cells |
|
When should you worry about a patient's hemoglobin level? |
When hemoglobin is under 8 The patient may require transfusion |
|
What makes AST and ALT? |
Hepatocytes |
|
Where is alkaline phosphatase made? |
In the bile duct |
|
Where is gamma-glutamyl transpeptidase made? And what may be the reason for it being high? |
In the bile duct ETOH |
|
If bilirubin is high, what should you be concerned about? |
An obstruction |
|
Is lipase or amylase more specific for acute pancreatitis? |
Lipase because amylase is also made by the salivary gland |
|
Why may a patient with obstructive pancreatic cancer have brown urine? |
Because bilirubin is in the urin |
|
What does glucose in the urine indicate? |
Diabetes An issue with the endocrine cells of the pancreas |
|
Why would a person with obstructive pancreatic cancer have bilirubin in the urine? |
Bilirubin is not getting to the gut where it needs to go and so it is backing up into the liver and then into the blood To compensate, the bilirubin is urinated out |
|
What is urobilinogen? |
Bilirubin is broken down into urobilinogen in the gut Urobilinogen gives feces its characteristic brown color |
|
Is urobilinogen normally found in the urine? Why? |
Yes Some urobilinogen is pooped out, some is reabsorbed and taken back to the liver to be reused, and any excess urobilinogen is removed by the kidney (normally a little is found in the urine) |
|
If there is not urobilinogen then how would this change the appearance of stool? |
This would cause clay colored stools |
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What does positive bilirubin and negative urobilinogen indicate? |
A blockage Bilirubin is not getting to the gut and is not being broken down into urobilinogen |
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What are some causes of obstruction that could preven bilirubin from getting to the gut? |
Gall stones and cancer |
|
Where are pancreatic cancers usually found in the pancreas? |
In the head |
|
Why does pancreatic cancer typically have a poor prognosis? |
Symptoms from pancreatic cancer do not usually present until late in the disease |
|
What happens in an ERCP? |
A scope goes to the duodenum, through the major papilla, and into the common bile duct Contrast is injected to help visualize the common bile duct |
|
How may the results of ERCP look in a patient with obstructive pancreatic cancer? |
Dilated bile duct from obstruction Stricture of the bile duct caused by a mass |
|
Is liver cancer typically a primary cancer? |
No, cancer from other sites is usually spread to the liver via the blood |
|
How does pancreatic carcinoma spread to the liver? |
through the bile ducts |
|
What is unique about the blood supply to the liver? |
The blood supply to the liver is dual (portal vein and hepatic artery) The portal system is not heavily oxygenated |
|
What is the role of the portal vein? |
The portal vein brings things in to the liver from the intestines, stomach, pancreas, and spleen to be filtered |
|
How is the liver organized? |
Contains a lot of lobules Lobules gather together and a central vein exists in the center of them |
|
What can disruption of lobule organization cause? |
Liver dysfunction |
|
What are sinusoids in the liver? |
Like little capillaries Come off the portal vein |
|
What are Kupffer cells? |
Like macrophages in the liver Surround the sinusoids |
|
What is the role of hepatocytes in the liver? |
Filter the blood and make bile |
|
What is the route of bile from the hepatocytes to the gall bladder? |
Hepatocytes > canaliculus > bile duct > gall bladder |
|
What is the role of the liver in carbohydrate metabolism? |
In a state of fasting, amino acids, glycerol, and lactic acid are used to make glucose (gluconeogenesis) If there is too much glucose, the liver can store it as glycogen (glycogenesis) When glucose is needed, glycogen can be broken down into glucose (glycogenolysis) |
|
Over time in the body, what is glucose turned into? |
Fat Goes to the bloodstream and/or is stored in adipose tissue |
|
How does the liver help to build proteins? |
Dietary proteins are broken down into amino acids > Amino acids will be used in the liver to make tissue or plasma proteins Amino acids can also undergo transamination (accepting of an amine group) or deamination (removal of an amine group) Transamination occurs to make glucose and nonessential amino acids Deamination occurs to make fatty acids, ammonia, and ketoacids Ammonia goes through the urea cycle to make urea Ketoacids generate ATP |
|
What cell type is ammonia most toxic to in the body? |
Neurons |
|
What does the liver do with fats? |
Dietary fats (triglycerides) are broken down into fatty acids > Fatty acids are broken down into 2 molecules of Acetyl-CoA by beta oxidation Acteyl-CoA is used in the citric acid cycle to make ATP HMG-CoA can convert Acetyl-CoA to cholesterol or bile salts, or lead to steroid synthesis |
|
How do statins work to lower cholesterol? |
Statins inhibit the conversion of Acetyl-CoA to HMG-CoA which inhibits cholesterol formation |
|
What do ALT and AST levels indicate? |
What is happening in the meat (bulk) of the liver |
|
Is ALT or AST or specific to the liver? |
ALT AST can also come from muscle, including the heart |
|
What is the normal ratio of AST to ALT |
AST is greater than ALT by two or three times |
|
When is AST more elevated? |
In alcoholics AST > 300 indicates alcohol |
|
When is ALT > AST? |
In fatty liver disease By 1000x in acute hepatitis, ischemia, toxins, autoimmune |
|
What are the major sources of ALP? |
Liver, bile duct, kidney, bone, placenta |
|
Where is GGT mainly from? |
The bile duct Can also be found in the liver (in the ER of cells) |
|
What two lab values are more indicative of excretory function of the liver? |
GGT and AP |
|
What is the average life span of a blood vessel? |
120 days |
|
What causes macrophages in the spleen to break down RBC? |
Breakdown of the RBC As the RBC travels through circulation it begins to breakdown and the macrophages recognize this the breakdown This occurs on average at 120 days |
|
How is conjugated bilirubin formed? |
Destruction of the RBC by macrophages in t he spleen > Heme and Globin > Globin is broken down into amino acids which are recycled and heme is broken down into iron and bilirubin (iron is recycled) > Bilirubin is made water soluble by pairing with albumin (bilirubin needs to be water soluble to get to the liver) > In the liver bilirubin is conjugated by the addition of glucuronic acid |
|
What are the three types of jaundice? |
Prehepatic or Hemolytic Jaundice (hemolytic anemia) Intrahepatic Jaundice (hepatitis) Posthepatic or Obstructive jaundice (gall stones) |
|
What happens in prehepatic or hemolytic jaundice? |
Occurs before the liver (ex. hemolytic anemia) Hemolytic anemia causes excessive breakdown of RBC which leads to increased levels of unconjugated bilirubin in the blood (the liver cannot keep up and conjugate the extra bilirubin) Feces will be normal or darker in these patients |
|
What happens in intrahepatic jaundice? |
Something going on with the meat (bulk) of the liver (Ex. hepatitis) Either: Increased unconjugated bilirubin in the blood because hepatocellular damage will prevent conjugation Or Increased conjugated bilirubin in the blood from inflammation which obstructs flow to the hepatic duct Feces color is variable |
|
What happens in posthepatic or obstructive jaundice? |
Ex. Gall stone Obstructed flow to the intestine causes backup to the liver and blood which increases conjugated bilirubin in the blood Stool will be a light color |
|
What is alcoholic liver disease? |
Most common cause of liver disease Initial change is a fatty liver > Alcoholic hepatitis (acute) > End-stage cirrhosis End-stage cirrhosis occurs in 10-20% of alcoholics AST > ALT |
|
How is alcohol absorbed? |
Alcohol can be directly absorbed from the stomach into the blood stream |
|
What is alcohol broken down into? |
Acetyl aldehyde and free radicals Acetyl aldehyde is very toxic |
|
What is alcohol specifically toxic to? |
The mitochondria (has a toxic affect on the electron transport chain) |
|
What does a fatty liver look like? |
Enlarged, soft, and yellow |
|
What would be seen on a biopsy of a fatty liver? Why would this happen? |
Vacuoles that contain fat Damaged electron transport chains cause increased levels of H ions which lead to a process of increased lipid synthesis inside the hepatocyte > accumulation of fat in vacuoles |
|
What do Mallory bodies on a liver biopsy indicate? What do they look like? |
Liver damage due to ETOH Pink worms |
|
What causes ascites? |
Cirrhosis Things can't enter the liver and get backed up The fluid leaks out because there is a volume overload in the patient (increased hydrostatic pressure) Increased hydrostatic pressure causes fluid to leave the vessels and lack of protein (albumin) causes the fluid to not be brought back in |
|
What are spider telangiectasia? What are they a result of? |
Dilated capillaries (will blanch with pressure) A result of cirrhosis |
|
What are esophageal varices caused by? |
Portal hypertension Rupture is a concern (especially from vomiting) Cirrhosis > things get backed up > vessels dilate > varices |
|
How does the liver appear in cirrhosis? What is this caused by? |
Granular Granulation is caused by nodules which are hepatocytes trying to regenerate and repair the liver Scar tissue forms between the nodules |
|
Why does jaundice cause yellow sclera? |
Bilirubin likes to bind to elastin fibers and there are many elastin fibers in the sclera |
|
What are some complications of end stage liver disease? |
Hepatic encephalopathy (due to elevated ammonia) Telangiectasia, spider nevi, purpura, palmar erythema Fibrotic liver changes Ascites Hemorrhoids Muscle wasting Edema Esophageal varices Gynecomastia (The liver breaks down hormones like estrogen so when the liver is not worked, estrogen is not broken down and results in gynecomastia) Splenomegaly (Spleen becomes large because is is congested; the spleen can also become hyperactive) Caput medusa Testicular atrophy Fetor hepaticus |
|
What are the results of splenomegaly caused by portal hypertension? |
Spleen is overactive Macrophages eat RBC (Anemia) The spleen gets congested and platelets get stuck (thrombocytopenia) Thrombocytopenia leads to bleeding WBC also get stuck (Leukopenia) |
|
What is the result of increased pressure in the peritoneal capillaries caused by portal hypertension? |
Ascites |
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What is the result of portosystemic shunting of the blood (blood getting backed up) caused by portal hypertension? |
Enlarged vessels (caput medusae, hemorrhoids, esophageal varices) Ammonia can't be broken down to urea which results in increased ammonia which causes hepatic encephalopathy Hepatic encephalopathy causes an altered mental status |
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What disorders of synthesis and storage functions can liver failure cause? |
Glucose > hypoglycemic events Proteins > Hypoalbuminemia (ascites) and/or decreased coagulation factors (bleeding) Lipoprotein and cholesterol > Decreased cholesterol Bile salts > Impaired fat absorption > deficiency of fat-soluble vitamins and fatty stools |
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What disorders of metabolic and excretory functions can liver failure cause? |
Amino acids > Impaired conversion of ammonia to urea > encephalopathy Steroid hormones > Increased aldosterone (Edema/ascites) and/or increased androgens/estrogens (gynecomastia and testicular atrophy in men and menstrual irregularities in women) Drugs > Drug interactions and toxicities Bilirubin > Hyperbilirubinemia > jaundice |
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What is the role of aldosterone? |
Aldosterone is a hormone made in the adrenal glands which causes your body to hold onto salt and water (causes swelling) |
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Do patients with end stage liver failure have hypernatremia? |
No |