Organism is resistant to acid – swallow it and will not die in presence of acid. It ex-cysts in the cecum, within an alkaline environment. Has a chemical that can drill a hole through the mucosa, leading to flask shaped ulcers, and leads to bloody
diarrhea. Unfortunately, b/c the cecum is drained by the portal vein, and is forming an ulcer, there is a chance that it can
drill and hole, get into the portal vein tributary and get to the right lobe of the liver, where it will produce an abscess. It will start dissolving the liver – hence term anchovy paste abscess b/c it looks like anchovy paste (a brownish liquid). If it wants to, it can drill a hole through the right diaphragm, go to the lungs, and produce an effusion, and go anywhere it wants in the systemic circulation – brain. Rx – metronidazole. Trophozoites (slide) with red particles in them, which are RBC’s. The only protozoa that can phagocytose is Entamoeba histolytica (no other amoeba can phagocytose RBC’s) – this is a very characteristic finding. Metronidazole is used in the treatment of giardiasis, Entamoeba histolytica, vaginosis, c diff, and trichinosis.
B. Hydatid dz
1. Definitive vs. intermediate host
Definitive host = sexually active worms that have the ability to mate and lay eggs. Intermediate host = only have the larval form; do not have sexually active adults.
These are the stages: Adult, egg, larva. Adult lays eggs, and the eggs develop into larva. If you have the larva form in you, it will stay there b/c that it’s the end stage form. If you have the egg form, it will develop into a larva, but the larva can’t go anywhere else. If you have the adult form in you, it will give an egg, which changes to larva. Larva form cannot go anywhere – it is the end stage form.
Sheep herder’s dz (gonococcus vermicularis or unilicularis (?))
The sheep dog eats some sheep meat (there are larval forms in the sheep; therefore, the sheep is the intermediate host). Dog eats sheep, and has larva in the dog. The larva form develops into an adult within the dog, and the dog becomes the definitive host. The dog has sexually active worms inside it and the worms lay eggs within the dog. Dog is petted, gets eggs on their hand and into pts food, which is eaten. So, now, the pt has the egg, which develops in the larva (cannot go any farther b/c larval form is end stage), and the pt (human) becomes the intermediate host. So, the sheep is an intermediate host, the dog is the definitive host and the sheep herder is an intermediate host. Do not want to rupture these cysts, b/c if the fluid gets into the abdominal cavity, leads to anaphylactic shock.
C. T. solium (pig tapeworm)
You go to a barbecue and eat undercooked pork (larva in the pig meat, which is eaten). The larva develop into the adult form within the pt (so, there is a sexually active worm inside). So, pt becomes definitive host, while the pig was the intermediate host. Now you have a family member that is a definitive host (has sexually active worms inside them) – lets say this family member is making salad that night, and didn’t wash their hands, so some of the eggs got into the salad. The pt eats the salad with the eggs in it. What is the egg going to form inside me? Larva. What is this called cystocerci. Do they form adults? No, stops there. Therefore, pt has cystocercosis. What are the larvae going to do? They like the eye
and the brain (where they form a cyst in the brain, calcify and lead to seizure activity for the rest of the pt’s life). So, in this dz, the pt can have two forms of it. If pt ate the infected pig, they can be the definitive host. If you get
the egg in your mouth, you become an intermediate host, and the egg can become larva, which will go on to cystocercosis. So the larvae form is the dangerous form in T. solium.
VI. Nutmeg Liver
MCC = RHF
Thrombus in portal vein will NOT lead to nutmeg liver because portal vein is before emptying into the liver. Would you have ascites? Yes. Portal HTN? Yes. Varices? Yes. But is liver big and congested? No.
Thrombus in hepatic vein: is called Budd Chiari syndrome (MCC polycythemia Rubivera, 2nd MCC = birth control pills). Would you have a nutmeg liver? Yes – hepatic vein empties the liver. You get a huge liver, and is a surgical emergency and die 100% of the time if you don’t have surgery.
So, these are pre/post hepatic thromboses (Prehepatic = portal vein, posthepatic = hepatic vein).
VII. Alcoholic liver dz
MC manifestation is fatty change (steatosis). B/c alcohol metabolism, have NADH’s, acetate, and acetyl CoA. NADH’s
mess with pyruvate and convert it into lactate leading to fasting hypoglycemia, and metabolic acidosis. Acetyl CoA can make FA’s and glycerol 3 phosphate and TG and fatty change, or can be converted into ketone bodies, which causes an increased anion gap: metabolic acidosis. Fatty change is reversible if the alcoholic stops drinking.
Alcoholic hepatitis is very bad; can have hepatic encephalopathy, ascites, etc. Alcoholic hep is diff from fatty change b/c there
is fever, neutrophilic leukocytosis, very high AST>ALT, and gamma glutamyl transferase is up. You’re big time sick and if you do not stop drinking you will die. It is very serious systemic dz. If pt hospitalized for alcoholic hep, is released and takes alcohol, they will die. See Mallory bodies (ubiquinated keratin microfilaments). Toxic compound that causes cirrhosis is acetaldehyde bound to a protein, not acetaldehyde by itself. Ito cell normally is the cell that stores Vit A. In an alcoholic the acetaldehyde protein complex stimulates the Ito cell to make fibrous tissue and collagen. The Ito cell, which is responsible for storing vit A, is now putting down collagen tissue and is responsible for causing fibrosis. Fibrous tissue is a big part of alcoholic tissue dz.
VIII. Cholestasis
Cholestasis = obstruction to bile flow, due to a stone in the CBD. Ex: have a cholesterol stone with a deep green colored liver.
Bile is blocked, which has conj bilirubin in it and is backed up into the liver. The conj bilirubin will eventually reflux into the sinusoids, and leads to bilirubin in the urine and light color stools, with NO urobilinogen in the urine. The yellow urine is due to water soluble conj bilirubin in the urine. What enzymes are elevated? Alk phos and gamma glutamyl transferase. What is the mech for getting rid of cholesterol? Bile. So, you reflux cholesterol, bilirubin and bile salts (they are all recycled). Would it surprise you that they have hypercholesterolemia, too? No b/c it is recycled. The bile salts deposit in the skin, leading to itching.
2 other causes of cholestasis:
Bile duct radical, surrounded by fibrous tissue, bloody diarrhea with LLQ crampy pain, jaundice – what is the IBDz? UC
Common bile duct surrounded by fibrous tissue – dx? Primary sclerosing cholangitis. MCC primary sclerosing cholangitis = UC
What cancer can develop b/c it involves the bile duct? Cholangiocarcinoma (MCC in this country, in 3rd world countries, it is due to Clonorchis sinensis – Chinese liver fluke).
IX. Primary Biliary cirrhosis
50 y/o woman with generalized itching, find enlarged liver on PE, normal bilirubin (no jaundice), alk phos and gamma glutamyl transferase are huge (obstructive type of enzymes), transaminases are elevated – dx? Primary biliary cirrhosis, which is an
autoimmune dz that leads to granulomatous destruction of the bile ducts in the portal triad – why doesn’t she have
jaundice? Let’s say you have 1 million triads, have the dz and knock off 250,000 of them. Still have 75% that can handle the bilirubin load. 3 years later, only have 50% (500,000 destroyed). Still no jaundice, eventually, more knocked off and get jaundice way down the line. So, the reason why pt won’t get jaundice is b/c pt has a reserve that can handle the bilirubin. Therefore, there is no reason to have jaundice early and it comes late. What is the Ab to order in this pt? Anti-mitochondrial
antibodies (antimicrosomal = hashimoto’s). X. Drug effects
Birth control (OCP) and anabolic steroid have the same effect on the liver. The OCP and anabolic steroids both produce
intrahepatic cholestasis. Ex. wt lifter (assume he’on steroids) develops jaundice, and viral serology is negative, high alk phos
and gamma glutamyl = due to steroids (not hepatitis). One of the MCC’s jaundice in pregnancy is b9 intrahepatic cholestasis. This is b/c of the estrogen during pregnancy, which produces intrahepatic cholestasis. Rx? Deliver baby (goes away after delivering baby). Lets say woman takes OCP and gets jaundice; when she become pregnant, she will develop jaundice, too b/c of the estrogen effect. So, intrahepatic cholestasis is a normal complication of OCP’s and anabolic steroids. Both of these
drugs also predispose to a b9 liver tumor, called liver cell adenoma aka hepatic adenoma. It has a nasty habit – it likes to rupture, leading to intraperitoneal hemorrhage (which can kill you). Example: wt lifter (assume he’s on
anabolic steroids) who is lifting and suddenly becomes hypotensive and collapses. Find abnormal liver/cavity – what is most likely cause? Ruptured liver cell adenoma b/c pt is on anabolic steroids. So, OCP’s and anabolic steroids have 2 similar
effects: both can produce b9 intrahepatic cholestasis (which goes away if you stop the drug) and liver cell adenoma which is susceptible to rupture. For women, if they are on birth control, then get off it to get pregnant – let’s say
they have a liver cell adenoma they did not know about (that developed with OCP use), then get pregnant, then get an intraperitoneal hemorrhage, and then what is d/d? Ruptured ectopic pregnancy or rupture intraperitoneal hemorrhage. Step 2: pregnant women have the tendency to have splenic artery aneurysm = rupture.
Example: hyperpigmented pt – adult that is diffusely hyperpigmented and has diabetes (type I diabetic) = bronze
diabetes = hemochromatosis = Fe overload, auto rec, reabsorb too much Fe. Hemosiderosis is acquired iron overload by
being an alcoholic. Iron supplements are contraindicated in the elderly b/c it will create hemosiderosis and have iron overload. Back to hemochromatosis: it’s an autosomal recessive dz and what happens is that instead of reabsorbing 10-15% of iron from foods, you are absorbing 100% of iron. Target organ is the liver. Whenever Fe is absorbed into cells, it produces hydroxyl free radicals. So, the Fe doesn’t damage anything, it’s the free radicals (the hydroxyl free radicals –Fenton rxn). If you are damaging liver cells, will lead to fibrosis and cirrhosis. They ALL have cirrhosis in Fe overload, either by hemosiderosis
or hemochromatosis. In cirrhosis, you see liver with brownish pigment, Prussian blue stain (to see Fe), and a VERY HIGH
incidence of hepatocellular carcinoma. Can also go elsewhere–pancreas–therefore can have EXOcrine and ENDOcrine dysfunction, leading to malabsorption. Destruction of islet cells leads to very brittle type I diabetes. Also deposits in skin and lead to hyperpigmentation (bronze look). This is a combo of Fe depositing there and by stimulating melanocytes, therefore there is Fe pigmentation and melanin. Can go into joints and lead to polyarthritis, can go to pituitary, leading to hypopituitarism, can go to heart and produce restrictive cardiomyopathy. How you do screen for iron overload? Serum
ferritin. Serum Fe = high. Excess Fe stores, therefore decreased syn of transferrin. The TIBC is decreased. % sat is increased, serum ferritin is increased. Rx? Phlebotomy. Do not use chelation therapy. They purposely make you Fe
def. This dz is the next to the most common autosomal rec dz. Hemosiderosis = ACQUIRED Fe overload – from alcohol.
XII. Wilson’s dz
Kayser Fleischer ring – brown ring around cornea. What is degeneration called? Hepatolenticular degeneration. Pt with abnormal movement (chorea) disorder, dementia, and cirrhosis. Auto recessive. Defect in ridding Cu in bile; so, the Cu builds up and accumulates in the liver. Very toxic. So, over a period of months to years, you go from chronic active
hepatitis to cirrhosis. When you get a total Cu level, what does it include? Free Cu and binding protein for Cu. The binding
protein is called ceruloplasmin. So, some Cu is attached to ceruloplasmin. So, the total Cu measured includes bound and
free. 95% of a normal total Cu level is related to Cu attached to ceruloplasmin. So, most of the total Cu level is bound to ceruloplasmin, not the Cu that is free. So, 95% in a normal person the total copper is Cu that is bound and inactive to
ceruloplasmin. So, is ceruloplasmin a protein? Yes. So, with cirrhosis, are you synthesizing ceruloplasmin? No. Therefore,
there is a decrease of binding protein for Cu. So, free cu increased. So, the total Cu level is decreased (b/c less
ceruloplasmin), but the free Cu is increased (more unbound). Rx? PCNamine (Cu binder). Lenticular nucleus messed up
(caudate nucleus in HD)
XIII. Cirrhosis
Never focal, always diffuse. The bumps all over it are called regenerative nodules. Know that liver tissue is stable, therefore it’s usually in the Go phase, and something has to stimulate it to go into the cell cycle to divide. The liver has an amazing regenerative capacity. Regeneration of liver cells are hepatocytes with no triad, no central vein, and no sinusoids. Just wall to
wall hepatocytes which are worthless. Bumps are regenerative nodules, no triad; there are just wall to wall hepatocytes
surrounded by fibrous tissue. Starts off as micronodular (less then 3 mm) and ends up macronodular (over 3 mm). So, have liver, but cells not working. How is a portal vein gonna be able to empty into the liver when there are no sinusoid/triads? It’s a problem – portal HTN.
Complications: Pitting edema, ascites, esophageal varices, and metabolic probs (cannot metabolize estrogen, leads to
gynecomastia). Cannot look at gynecomastia, have to feel it.
Side effects of problems of estrogen metabolism: Side note: There are 3 times in a lifetime where males can develop
gynecomastia. 1. Newborns males have boobs b/c estrogen from mom; newborn girls with periods b/c estrogen from, then drop off, leads to bleeding. 2. Males also get boobs in teens (puberty). 3. Males also get boobs when they turn old b/c testosterone goes down and estrogen goes down, leading to gynecomastia – so, get boobs (gynecomastia) three times throughout life, and this is normal. Example: 13 y/o unilateral subalveolar mass, what is management? Leave it alone. Gynecomastia is not always bilateral, it is usually unilateral. Women have diff size breasts b/c each breast has different susceptibility to estrogen, progesterone, and prolactin. Men do not have breast tissue, therefore more likely that one will enlarge, the other will not. Palmer erythema (related to estrogen), spider angioma, vit def’s, dupatron’s contracture in palm (fibromatosis – increased fibrous tissue around the tendon sheaths, causing fingers to coil in, commonly assoc with alcoholics) – these are all estrogen abnormalities.
Complication of Ascites – adult with ascites – spontaneous peritonitis due to E coli. Child with nephrotic syndrome and get ascites and spontaneous peritonitis, what is the organism? Strep pneumoniae. So, adults with ascites and spontaneous peritonitis = E coli, while kid with ascites and spontaneous peritonitis = Strep pneumoniae.
XIV. Hepatocellular carcinoma
Nodularity; Cancer in hep vein tributary (ie). This cancer almost always develops in the background of cirrhosis. It is very rare for hepatocellular carcinoma to develop without cirrhosis present. Since alcohol is the MCC’s cirrhosis, is it also the MCC of cancer? NO. MCC’s hepatocellular carcinoma = pigment cirrhosis: hemochromatosis; hepatitis B and C. This cancer can produce ectopic hormones – EPO (leads to 2ndary polycythemia), insulin like GF (leads to hypoglycemia). Tumor marker: alpha feto protein. Example: pt with underlying cirrhosis, and is stable. But suddenly the pt begins to lose wt and ascites is getting worse. Do a peritoneal tap and it is hemorrhagic (do not assume it is traumatic from the needle, unless they say it). If there is blood in the acidic fluid it is pathologic bleeding. So, this hx (wt loss, beginning to deteriorate suddenly, blood in
acidic fluid). Know it is hepatocellular carcinoma, but will ask – what test do you do? Alpha feto protein. Many
tumors in liver = mets, prob from lung; lets say it’s a nonsmoker, what is the primary cancer? Colon cancer, b/c he is a nonsmoker, therefore it won’t be from a primary lung cancer, so the 2nd MCC is colon cancer and it doesn’t have a high association with smoking.
Remember the 2nd most common cause: example of a small bowel obstruction, the MCC is adhesion from previous surgery, but if the pt did not have any surgeries then it’s due to indirect inguinal hernia.
GALLBLADDER DZ
I. Ask about pathogenesis of stone – too much cholesterol in bile or too little bile salts. You will have a supersaturated
stone with cholesterol – will get cholesterol stone (MC stone). Or, too little bile salts, both lead to stones. Anything that causes bile salt def (cirrhosis, obstruction, Cholestyramine, Crohn’s dz) can lead to gallstones b/c too lil bile salts.
II. Pigment stones
Yellow stones (know they are not cholesterol stones) – 25 y/o female, RUQ crampy pain, fever, point tenderness, neutrophilic leukocytosis, stones revealed on ultrasound. CBC showed a mild normocytic anemia and a corrected reticulocyte ct of 8%. Splenomegaly on PE and family hx of splenectomy. Dx? Congenital spherocytosis; b/c she has been hemolyzing RBC’s all her life, she puts a lot of bilirubin into conj bilirubin and therefore has supersaturated bile with bilirubin, and forms Ca bilirubinate
stones that are jet black. Seen with ultrasound.
What is the screening test of choice for stones? Ultrasound. Screening test of choice for anything in the pancreas = CT – reason why is b/c bowel overlies pancreas and messes up ultrasound, therefore not as sensitive. Always put CT for pancreas; GB = ultrasound (can tell diameter of CBD to tell if there is a stone in it).
PANCREAS