[Discussion] Hepatic Metabolism of Oral AAS, Hepatotoxicity, and Liver Support
I know this is a long write up, the first half is biochemistry and what happens on a cellular level. The second half is more pertaining to the average AAS user, including a deeper dive into liver functioning tests and liver support. I highly recommend at least reading the second half, especially the Liver Support section. Hepatotoxicity is a word that is frequently thrown around, everyone’s heard it, everyone thinks they know what it is, but once you ask something beyond surface level, you get a whole lot of conflicting answers. Let’s dive into it. Overview/Background/General Information/What the fuck actually happens? Drug Metabolism: The human body identifies almost all drugs as foreign substances and subjects them to various chemical processes to make them suitable for elimination. Drug metabolism is typically split into two phases: Phase 1 (oxidation via Cytochrome P450, reduction, and hydrolysis) tends to increase water solubility of the drug and can generate metabolites. Phase 2 further increases water solubility of the drug, inactivating metabolites, thus preparing it for excretion.
Aside: There has been a lot of questions regarding using high dose psoralens (from grapefruit juice/extract) to inhibit the activity of Cyp3A4 (and the Cyp450 family in general) or consuming large quantities of chargrilled meat to induce the activity Cyp450. DO NOT purposely do this in an attempt to increase the bioavailability of oral steroids. The Cyp450 family is incredibly important enzyme family that is involved in the metabolism (both activation and degradation depending) of statins, oral contraceptives, acetaminophen, anti-depressants, beta-blockers, antiarrhythmic agents, and many, many more. This can cause SEVERE adverse effects.
Example: Acetaminophen (Tylenol) is often seen as hepatotoxic, it is not. One of the metabolites, NAPQI, is. Under normal conditions, NAPQI is produced in incredibly minor amounts. Alcohol induces Cyp450 enzyme family, which increases the breakdown of Tylenol into NAPQI, causing intensive acute liver damage which can often be fatal in high doses. In short, don’t nurse your hangover with Tylenol, use Advil instead… or better of just don’t drink alcohol.
17α-Alkylated Anabolic Steroids. These AAS contain a methyl or ethyl group on the C17α position, allowing for oral activation. This modification allows the drug to survive hepatic metabolism, limiting the amount of steroid that is broken down, allowing for more drug to reach the bloodstream. Without this modification, the drug is completely broken down by the liver, never reaching systemic circulation. This initial process is called First Pass Metabolism. First pass metabolism: After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. It is carried through the portal vein into the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver may greatly reduce the bioavailability of the drug. Some oral steroids have a very low bioavailability due to first pass metabolism, thus injectable versions may be used to prevent the initial breakdown, effectively increase bioavailability and reducing liver stress.
Aside: There have been questions regarding sublingual administration of oral AAS in order to bypass first pass metabolism. In short, very few drugs can be properly absorbed sublingually, Nitroglycerin is a prime example. AAS, although can be manufactured for sublingual absorption it requires a specific method of delivery (sublingual tablets, strips, or sprays for example), which are difficult to obtain and manufacture; it’s not as simple as placing some powder under your tongue. Other drawbacks exist of sublingual administration such as tooth decay and difficulty in dose management.
Anavar: The exception to the rule: The oral bioavailability of oxandrolone is 97%. The drug is metabolized primarily by the kidneys and to a lesser extent by the liver. Oxandrolone is the only AAS that is not primarily or extensively metabolized by the liver, and this is thought to be related to its diminished hepatotoxicity relative to other AAS. For this reason, there is no reason to ever use injectable anavar (unless poking yourself that often is your kink, no judgement).
[aside: not all drugs are orally active, in fact the majority are inactive. For example, codeine (inactive) will be converted into the active form, Morphine, within the liver via Cyp450 enzymes]
In the case of oral AAS, hepatic metabolism can convert an active drug into its inactive form; C17α methylation prevents this. Why is this modification known to be hepatotoxic? The primary enzyme that normally breaks down hormonal steroids (such as endogenous DHEA, testosterone, estradiol, etc) is 17β-Hydroxysteroid dehydrogenase, 17β-HSD, (and to a minor extent the Cyp450 family) which can no longer break down the methylated drug, thus the liver finds an alternative route for metabolism. The actual specific process is still relatively unknown, but involves a variety of oxidation reactions, inducing an increase of free oxygen radicals within the hepatocytes (liver cells), causing cell death due to oxidative stress. There is another hypothesis which involves the presence of androgen receptors within the liver. The C17α methylated oral steroid, that is no longer properly broken down, will bind to these receptors, causing a drastic increase of androgenic activity within the liver, leading to hepatoxicity. In my opinion, it is a mixture of both. Many studies show a direct correlation between the androgenic effect of the oral steroid and the amount of hepatoxicity. The exact link between the two is yet to be determined. In general, the greater the affinity of C17α methylated oral steroid for the androgen receptor, the more hepatoxicity occurs.
Hepatotoxicity is an overlying term: the specifics related to AAS use are Cholestasis (blockage of biliary flow), Steatosis (accumulation of fatty lipids within the liver), Zonal Necrosis (hepatocyte death within a specific zone of the liver), and Peliosis Hepatitis (vascular lesions leading to liver enlargement).
Aside: Steatosis (fatty liver) has been an observed adverse effect of Nolvadex and Raloxifene
Cholestasis is a condition where bile cannot flow from the liver to the duodenum. It is the most common condition resulting from oral AAS use. In short, bile is continuously produced but cannot leave the liver, causing build up, backflow, and eventually hepatocyte death. Differential symptoms of cholestasis include but are not limited to pruritus (itchiness), jaundice (yellowing of the skin and whites of the eyes), pale stool, and dark urine. Liver Functioning Tests: What do they mean and why are they relevant? AST: Aspartate Transaminase: This alone is not a good indication of liver damage. AST is found in abundance within both cardiac and skeletal muscle. An elevated AST value can be caused by something as minor as weightlifting. ALT: Alanine Transaminase: ALT is found specifically within the liver and is released into the plasma when significant liver stress, including hepatocyte death, occurs. An elevated value is of concern.
Aside: general rule of thumb (not always true) if both elevated are elevated and if AST>ALT in a ratio of 2:1, suspect alcohol/drug induced damage. If both values are elevated and if ALT>AST in a ratio of 2:1, suspect viral hepatitis.
ALP: Alkaline Phosphatase: ALP is found within the hepatobiliary ducts. An elevated value is commonly indicative of obstruction and bile buildup, signifying cholestasis. GGT: Gamma-glutamyl Transferase: GGT is an enzyme that is found in many organs throughout the body, with the highest concentrations found in the liver. GGT is elevated in the blood in most diseases that cause damage to the liver or bile ducts. 5’-nucleotidase: The concentration of 5’-nucleotidase protein in the blood is often used as a liver function test in individuals that show signs of liver problems. ALP can be elevated due to both skeletal disorders and hepatic disorders. 5’-nucleosidase is elevated ONLY with hepatic stress, not skeletal, thus allowing for differentiation.
Putting it all together: Cholestasis can be suspected when there is an elevation of both 5'-nucleotidase and ALP enzymes. Normally GGT and ALP are anchored to membranes of hepatocytes and are released in small amounts in hepatocellular damage. In cholestasis, synthesis of these enzymes is induced, and they are made soluble. GGT is elevated because it leaks out from the bile duct cells due to pressure from inside bile ducts. As hepatocyte damage continues, ALT, AST, and unconjugated bilirubin will begin to rise. In short: Initial liver stress causes 5’-nucleiotidase and ALP to rise, shortly after GGT rises, then finally AST and ALT rise. Thus, with only AST and ALT values, it is difficult to determine the cause and extent of hepatic damage. Liver Support: NAC/TUDCA/Liv52 NAC: N-Acetyl Cystein NAC is a prodrug of L-cysteine, a precursor of the biological antioxidant glutathione which is able to reduce free radicals within the body. Free radicals, which as discussed above, are associated with causing extensive hepatocyte damage due to the oxidative breakdown of C17α methylated AAS. In addition to its antioxidant action, NAC acts as a vasodilator by facilitating the production and action of nitric oxide. This property is an important mechanism of action in the prophylaxis of contrast-induced nephropathy and the potentiation of nitrate-induced vasodilation.
Aside: NAC has been constantly used as an adjunct to multiple neurological disorders including Parkinson’s, Huntington’s, Multiple Sclerosis, Cerebral Ischemia, Alzheimer’s and MANY more due to the potent free radical trapping effect which prevent mitochondrial dysfunction.
Multiple studies have constantly showed NAC decreasing liver functioning tests and improving liver function and mitigating cholestasis. NAC had the ability to vastly improve markers of kidney function and was actually able to even double the rate of sodium excretion, indicating that NAC is may be useful in preventing water retention. In short, NAC has a vast number of benefits, including hepatoprotective (liver), nephroprotective (kidney), and neuroprotective (neural), and anti-inflammatory effects that have been constantly demonstrated thru literature. Moreover, NAC can and should be used for year-round support since the adverse effects are incredibly mild. There is absolutely NO reason to not be taking NAC.
TUDCA: Tauroursodeoxycholic acid TUDCA is a bile acid taurine conjugate form of UDCA. As discussed above, during cholestasis, bile builds up, creating backflow and inducing hepatocyte death thru apoptosis. Apoptosis, or programmed cell death, is largely influenced by the mitochondria. If the mitochondria are distressed, they release the molecule cytochrome C. Cytochrome C initiates enzymes called caspases to propagate a cascade of cellular mechanisms to cause apoptosis. TUDCA prevents apoptosis with its role in the BAX pathway. BAX, a molecule that is translocated to the mitochondria to release cytochrome C, initiates the cellular pathway of apoptosis. TUDCA prevents BAX from being transported to the mitochondria, effectively inhibiting hepatocyte death. Furthermore, TUDCA aids in the processing of toxic bile acids into less toxic forms, resulting in decreased liver stress, further preventing hepatocyte death. Moreover, TUDCA aids in the transport of bile from the liver into the duodenum, effectively unblocking the build up causing cholestasis. Finally, TUDCA has been proven to be an effective treatment for the necro-inflammatory effects of Hepatitis. Study after study has shown that TUDCA greatly improves liver enzyme values. Why do we recommend only using TUDCA with hepatotoxic oral steroids? The idea is that TUDCA induces liver damage when there is no hepatotoxicity present… but after reading the above, does that make sense? It does not. I could not find any literature showing that TUDCA induces liver toxicity. The recommendation instead is due to the negative effects of TUDCA on cholesterol values. TUDCA has been shown to greatly decrease HDL levels when taken for extended periods of time. The idea is, if you have a healthy functioning liver, there is no reason to take TUDCA for long periods of time since all you’re doing is decreasing HDL values. That being said, after doing the research and seeing the vast benefits of TUDCA (included bellow, not a comprehensive list), I am beginning to change my perspective on TUDCA use with only hepatotoxic oral AAS. In short, TUDCA prevents hepatocyte death, enhances hepatocyte function, exhibits anti-inflammatory effects on the liver, neutralizes toxic bile, and prevents bile build up that was caused by the alternative metabolism of C17α methylated AAS. ***THERE IS NO EVIDENCE THAT I HAVE COME ACROSS THAT SHOWS THAT TUDCA ITSELF INDUCES LIVER DAMAGE WHEN USED WITHOUT HEPATOTOXIC DRUGS**\* TUDCA has a variety of other benefits outside the liver, but I will not go into them this time. In short:
Increasing glucose-induced insulin release via the cAMP/PKA pathway, increasing insulin sensitivity.
Relieving endoplasmic reticulum (ER) stress. The ER makes sure proteins are folded properly.
Reducing programmed cell death (apoptosis) in healthy cells. TUDCA prevents the molecule BAX from reaching the mitochondria. BAX causes mitochondria to release cytochrome C, which causes enzymes (caspases) to initiate apoptosis.
Inactivating Bcl-2-associated death promoter (BAD), a molecule involved in apoptosis.
Removing toxic bile acids from the liver and preventing them from damaging liver cells
Exhibits neuroprotective effects via the inhibition of NF-kB
Preserve photoreceptor function and increases retinal health by increasing rd10
Liv52 Liv52 is an herbal liver support. There have been medical studies conducted on Liv.52 in recent years, many of which involve its ability to protect the liver from damage by alcohol or other toxins. Liv52 has been shown to exhibit antiperoxidative function, antioxidant effects, anti-inflammatory, diuretic effects and neutralization of toxic products within the liver. “The results demonstrated that the patients treated with Liv-52 for 6 months had significantly better child-pugh score, decreased ascites, decreased serum ALT and AST. We conclude that Liv-52 possess hepatoprotective effect in cirrhotic patients. This protective effect of Liv-52 can be attributed to the diuretic, anti-inflammatory, anti-oxidative, and immunomodulating properties of the component herbs.”
“Liv.52 enhanced the rate of absorption of ethanol and rapidly reduced acetaldehyde levels, which may explain its hepatoprotective effect on ethanol-induced liver damage.”
“Liv.52 administration reduced the deleterious effects of ethanol. The concentration of acetaldehyde in the amniotic fluid of ethanol-consuming animals was 0.727 microgram/ml. Liv.52 administration lowered it to 0.244 microgram/ml. The protective effect of Liv.52 could be due to the rapid elimination of acetaldehyde.”
That being said, there is conflicting research on Liv52. The studies either show hepatoprotective function or no effect, positive or negative. “There was no significant difference in clinical outcome and liver chemistry between the two groups at any time point. There were no reports of adverse effects attributable to the drug. Our results suggest that Liv.52 may not be useful in the management of patients with alcohol induced liver disease.”
In short, Liv52 can be used if you have the additional funds, it is not the end-all-be-all but can be used as an adjunct. It is an incredibly cheap drug thatmayimprove liver function and exhibit hepatoprotective effects. IT SHOULD IN NO WAY YOUR ONLY LIVER SUPPORT MEDICATION, but there is nothing wrong with using it.
Age : 18 Sex : F Race : Caucasian Weight : 65.5kg/144lbs Height : 164cm/5.5ft Existing conditions : ADHD Current medication : Concerta LP 54mg Drug use : none Smoking : no Hello, I am about to start isotretinoin so my dermatologist prescribed a routine blood test to check my cholesterol, my bilirubin and my hormones. It was the first time in my life that I had a bilirubin check. When the results came back this afternoon, everything was normal (cholesterol, ASAT, ALAT) except my bilirubin levels which were abnormally high :
total bilirubin (plasma) : 17.7 mg/L or 30.3 μmol/L
conjugated bilirubin (plasma) : 4.3 mg/L or 7.4 μmol/L
un-conjugated bilirubin (calculated) : 13.4 mg/L or 22.9 μmol/L
The thing is, I have absolutely no symptoms other than fatigue, and sometimes when i don't sleep or eat well, the corners of my eyes get slightly yellowish. This usually disappears in 2-3 days. I don't have a fever, no pain, no nausea, no migraines, nothing ! I was told it could possibly be Gilbert syndrome, but I have no idea if it adds up or not... I just want to know if this is a possibility. Thank you for reading
Hi all! I recently had my yearly check-up and my total bilirubin was 3.2 mg/dL. Since it was elevated, my doctor ordered another blood test last week to get a breakdown of the bilirubin (I'm assuming to see the direct/indirect bilirubin levels). I'm still waiting on the results of that blood test, but I was doing some reading about elevated bilirubin levels and I came across some info that said if bilirubin is present in the urine then the elevation is probably caused by direct (conjugated) bilirubin. That means the absence of bilirubin in the urine points to the total bilirubin being made up of indirect (unconjugated) bilirubin. It also said that the absence of urobilinogen points to direct bilirubin levels being high, while normal urobilinogen levels are a characteristic of high levels of indirect bilirubin. I was wondering if this was true for those of you who have been diagnosed with Gilbert Syndrome. My urine was negative for bilirubin and the urobilinogen was normal, so I'm leaning towards the breakdown probably showing mostly unconjugated bilirubin and being Gilbert Syndrome.
Ok so I (26, male) have had very strange chest pains since September 2019. Went to the hospital a couple times and my liver enzymes were always elevated. In February of 2020 I got a copy of the following letter: “Just a quick update regarding this patients results. Liver ultrasound scan has been normal, MCRP scan shows normal bile ducts. Liver screen, including extended auto-antibodies, is unremarkable. Gamma-GT is 17, and while bilirubin is slightly high at 27, conjugated bilirubin is normal at 9, suggesting a component of Gilbert’s syndrome. Alkaline phosphatase is 170, the pattern is suggestive of an extra hepatic source, likely bone. I am enclosing blood forms for Vitamin D and for ALP isoenzymes with Mr redacted’s copy of this letter for him to get done soon. We will see him back in our liver clinic in due course with the blood results.” Fast forward to July of 2020 and because of covid I’ve been laying low at home. I haven’t stepped outside a lot at all which worries me considering the vitamin D shout. Especially since there seems to be a direct link in the severity of the disease in those with a vitamin D deficiency. What’s worrying to me is the fact that I’ve been working the night shift for the past two years and have avoided a lot of sunlight during UVB hours (10am - 3pm). This, unbeknownst to me then, probably caused my mild depression. I ate a lot of junk food and lived a very sedentary lifestyle. Although I never looked fat at all so I guess that’s why I didn’t portion my meals. However ever since September 2019 I’ve been eating very clean and went from ~ 20% body fat in February to probably ~10% body fat. I also take around 7 ~ 10k steps every day. List of symptoms: chest pain, cold/tingling feet and hands. Smelly feet even if I wash them 3 times in a day. Eyes that become bloodshot after walking ~30 mins. Random dizziness etc. Lumps on my chest and lower back, feel sensitive to touch. Last one is probably the most concerning. But I’ve had chest x-rays and an MRI scan done so surely this should’ve been picked up? I wrote a lot, but all in all I’m lost. I’m too afraid to go to the GP or hospital because of covid. I’m trying my best to escape reality by keeping my mind occupied, but every now and then I’ll feel pain that snaps me back to reality.
Trace simple free fluid in Right lower quadrant with abdominal pain?
Age: 31, Weight: 125lbs, Male, 5'8, Caucasian. Hello all, I am very concerned about some abdominal pain I've had for about 2 months. During the quarantine I was overeating dinner almost every night, which would lead to cramping and congested feeling in my liver. I eat very healthy, exercise, and am otherwise appear healthy, I was just overconsuming food. After a month of this stress eating, the pain seemed to lower down to just to the right of my naval, and it stayed there for longer and longer episodes of the day, usually right after eating. It seems to go away during a fasting state, and peaks between 1-8 hours after eating. It's a dull ache, and it usually comes with indigestion, even small, simple meals. It can even trigger with beverages or if I drink too much water. I've lost about 5lbs. and some muscle mass. I went to my primary care doctor, who did a CBC, metabolic panel, and urine test. Here are the things that stood out to her: Bilirubin: 2.7mg/dL (I have chronically elevated Bilirubin, it has gone from 1.8 to 2.2 to 2.7 now over the last 2 years. The conjugated Bilirubin was 0.3 last time we checked, about a year ago, which lead my doctor to think it was probably genetic.) White Blood Cells: WBC 4.04 103/uL Normal Range: 4.3 - 10.0 103/uL Neutrophils 1.66 103/uL Normal Range: 1.80 - 7.00 103/uL She wanted an ultrasound, and the results were non-remarkable. There was a small amount of debris in my gallbladder but no signs of cholycystitis. The thing that really scared me was the discovery of "Trace simple free fluid" in my lower right quadrant, right around the area that the pain has settled. The radiologist told me that "Some people have that, it'll probably be okay". Looking this up online, isn't that ascites, which is 75% likely to be cirrhosis and 10% various cancers? I can't find anything saying that is normal, or even anything that there's anything greater than a miniscule chance that it's not completely terrible. But "The liver was normal in size and echotexture. 12.5cm Main portal vein hepatopetal." my liver enzymes were "perfect" according to my doctor. This leads my worries to cancer, especially with the lower White Blood Cell count. I was told that I could get a CT scan, but I'm concerned that if it IS cancer, the radiation is just going to make the issue worse? And I'm highly sensitive to all chemicals, and my Mother had a bad allergic reaction to the contrast dye before. I do have a family history of GI problems, usually idiopathic, all very similar to this. Almost everyone in my family. But I'm very concerned, and I have no idea why the radiologist just hand waived the fluid away, it seems like it could potentially indicate a very big problem. Can anyone reassure me that this is something probably normal, or should I seriously consider the CT scan?
Me - 42 year old female, 140 lbs, in overall good health, 2 recent pregnancies, 1 C-section. I've had unexplained itching on my entire body for years, about 7 long years which has affected my quality of life. I've been health conscious for over a decade and shop at the health food store, take whole food multivitamins, probiotics, vegan diet, lost weight on my own about 35 lbs 8 yrs ago (though gained weight after my 2nd pregnancy), drink lots of water, non-smoker, no alcohol or soda, use non-toxic products on my skin, hygeinic products and laundry detergent, and am on no meds (aside from 1 for my gallbladder I just started 1 month ago). I've seen numerous doctors and dermatologists, and went to the ER. I initially attributed it to my cat, something zoonotic or parasitic, mites or scabies with no rash. Interestingly, a few of my family members claimed they had itching too after coming into contact w/me, furthering my suspicions of something scabies-like on my skin. It started as intense itching localized in my nostrils, then spread across my entire body. Most doctors dismissed what I was saying, finally got a derm to do a skin scrape only to find demodex mites (but everyone has them in their microbiome). I was tested for autoimmune diseases like lupus, negative. I took 2 doses of Ivermectin, was prescribed steroid creams and permethrin cream, bathed in Epsom salt, borax, vinegar, used rubbing alcohol -- didn't work. I've had tons of blood tests, got pregnant twice and had 2 babies in 2017 and 2019. The entire duration of my prenatal care I told doctors of my pruritis, and had many blood tests. Still, no one helped pinpoint my problem. Nothing was mentioned like intrahepatic cholestasis in pregnancy or my gallbladder or my liver, as I just found out last month, by way of another ER visit, that I have multiple gallstones and did have impacted stool. I realized I had been constipated for a LONG time and was not doing anything about it. I had a gallbladder attack and was on morphine for days, one stone was in the cystic duct. My CT scan was great aside from gallstones, and I believe 1 tiny kidney stone. Interestingly, I have been vegetarian/vegan and on a low-fat diet for 12 years and my cholesterol is only 145. Though, I do eat vegan processed foods and oils in those are fatty. I come to find out that prolonged low-fat diets can cause stones apart from fatty foods on the Standard American Diet (SAD)because supposedly only fatty foods trigger the gallbladder to release bile, therefore bile pools and conjugates in the bladder and forms stones. I was scared to death of getting a MRI due to claustrophobia, thankfully I found another hospital that has a wider bore machine and got the MRCP done. There I was jaundiced w/high bilirubin, diarrhea, pale stools, malaise, high liver enzymes, and did the ERCP endoscopy that removed several stones in my bile duct and duodendum and had mild pancreatitis. The GI doc confirmed they were stones made of cholesterol. I backed out of cholestectomy as my liver enzymes were lowering and I had no pain whatsoever my entire hospital stay, and am now on ursodiol hoping to shrink and dissolve stones. I also want to try lithotripsy combined with ursodiol. Follow-up bloodwork showed my liver enzymes were almost back to normal, but weeks later I still have tenderness in the liver area. No pain, just tender. I felt so much better after the ERCP but I still am itching. I read that low bile flow can cause it, but can gallstones themselves? I did experiment w/ox bile, chanca piedra, d-limonene, garlic oil extract, Stone Free herbal solution. I've read lots of medical journals on how to dissolve stones and know there are other ways to preserve the gallbladder via surgical methods which eliminate stones, even found surgeons in China that advocate for it. I know the standard of care is cholestectomy but your body can still form stones after removing the gallbladder or post cholestectomy syndrome. I'm now concerned about things like primary sclerosing cholangitis, etc. or something going on with my liver and its been very difficult finding a GI doctor that takes my insurance. I'm also looking for a hepatologist. This has been 7 long years, literally the 7-year itch. Will I finally solve this mystery?
Apologies if this is too much unnecessary information. ME: 29M, 290lbs, 5' 9, mix black/hispanic; palpitations with trouble breathing; on and off 2 years; cause unknown; 3.6cm liver lesion detected with CT scan with contrast declared most likely benign, ALT 79; No drugs/drinking/smoking/vaping; Prescribed metoprolol Part 1: Weight loss and initial heart problems Had a huge weight loss few years back 250lbs -> 185lbs, started gaining it back in a year and at the end of 2017, ~250lbs again, I was suffering from palpitations and sudden shortness of breath. I went in and out ERs and everything was more or less normal except for an elevated heart rate that hit 150-160 while just lying in the hospital bed. At the end of the journey I had several ekgs, an echocardiogram, and was given a ZIO patch to monitor my heart rate. EKGs and echo normal, no reason for tachycardia epsiodes found but there were abnormal events while wearing the ZIO patch. I had an episode of an extremely low HR (for me who usually sits in the 80s) when it plummeted to 34bpm the pulse ox i had at the time read an extremely low oxygen level (I feel like it was in the 70s but it's been a while) which freaked me out and then my heart rate sky rocketed to compensate. I had a few more episodes of my heart rate hitting 150-160 with no obvious cause. I was prescribed metoprolol and told to see if it continues or gets worse. Part 2: Intermediate period, weight gain It got a lot better I stopped taking metoprolol, I carry baby aspirin all the time and take it if I feel wonky which happened rather sparingly. Regrettably did not pursue follow up with cardio. I developed what I assume is a tick during this period, I inhale air suddenly and belch it out looked it up and it seems I'm swallowing air suddenly and immediately burping it out, usually happens infrequently but when nervous or sitting for long periods it becomes more frequent. Does not occur when sleeping, occurs less when talking, occurs very frequently while anxious/nervous. I feel down on myself and dieting and end up gaining 40lbs (290lbs current weight) which I didn't discover until last night because I don't use the scale anymore. Part 3: No heart answers, Liver lesion One or two more high HR episodes and I've been taking more baby aspirin over the past month or two and then last night I get a big one while eating, I feel like my face is tight and like I'm not getting enough oxygen I use my pulse ox and my oxygen is dropping and hits the high 80s and then my HR skyrockets to compensate and I hit 180 bpm. Double whammy of a high heart rate, being nervous because of a high HR, and being home alone so I call an ambulance. EMT says my blood pressure was ~150/~110 (i feel like it was 153/109 but I cannot remember exactly) but blood pressure after I left ER settled down to 109/71. Battery of tests to find out what's going on again and everything comes out normal just like it usually does, this time my heart rate never got lower than 99bpm even though I stayed there from 8PM ~ 3AM. Oxygen is intermittently a little low, at least from looking at my pulse ox, I get 91-93 oxsat in my worst moments during my stay otherwise it's normal at 94-98. They order a CT scan with contrast of my chest, everything looks fine but they noticed a lesion on my liver the doctor said he thinks it's benign but that I need to follow up with my PCP and cardiologist since they still don't know why I get these heart episodes. He says it may simply be anxiety, prescribes metoprolol but tells me to wait a day or two before I start taking it to see if my heart finally settles below 100. When resting in bed I check my heart rate and I've successfully hit 83. I read my bloodwork and their report and now I can't help being anxious about the state of my liver, the lesion is 3.6cm and one of them noted hepatic steatosis. Now I'm worried about my follow up and I feel like I compounded my health problems by eating myself fatter than when I was already too fat, I cannot help but contemplate the possibility of liver cancer despite how the doctor seemed unconcerned. And now I realize if I don't lose weight I'll destroy my liver, I've never felt guiltier for breaking my diet. In fact ever since gaining all the weight back I've never physically felt so miserable. Liver tests: ALBUMIN 4.4 g/dL BILIRUBIN TOTAL .3 mg/dL BILIRUBIN, CONJUGATED <.2 mg/dL ALKALINE PHOSPHATE 113 u/L ALANINE AMINOTRANSFERASE (ALT) 79 u/LNOTED AS HIGH ASPARTATE AMINOTRANSFERASE (AST) 43 u/L PROTEIN TOTAL 8.2 g/dL NOTED AS HIGH Everything else in bloodwork came back as in normal ranges except for MONOCYTE COUNT 0.8 k/uL NOTED AS HIGH Quotes from imaging: "3.6 cm hypervascular lesion in the right lobe of the liver, incompletely characterized on this exam. A benign etiology is favored, but the lesion is ultimately indeterminate. Nonemergent MRI can be obtained for definitive characterization." "There are no enlarged mediastinal, hilar or axillary lymph nodes.The visualized portion of the thyroid gland is unremarkable. Anterior mediastinal soft tissue density likely represents benign thymic tissue.Images of the upper abdomen demonstrate hepatic steatosis There is a 3.6 cm a prevascular lesion in the right hepatic lobe." Per recommendation I've already scheduled a meeting with my PCP on the 12th, I want to try and schedule another visit earlier (if possible) with another doctor that accepts my insurance. Also per recommendation I want to schedule a meeting with my cardiologist although if possible I'll take any appointment that's earlier (in addition to the one who knows me). I would like any advice or analysis. On doctor visits and testing: Is it pointless to visit a doctor that can fit me in (if i can find such a doctor) before my pcp? I feel like I need to schedule an MRI asap to get this lesion verified. What should I be asking my doctors? What tests should I get or not get? How concerned should I be? What should I ask my cardiologist? What's the best thing for me to do as a patient? Is there anything I should look for when picking a doctor? On weight loss: I cannot do what I first did to lose weight over concerns with my heart, my restriction to 1000 calories per day when I first lost weight was too strict and in that weight loss period I had scheduled a month for fasting which I view as impossible with my current heart. On mental state: I don't consider myself an anxious person but I may just lack perspective on that, however I can't help but think any kind of lesion is cause for concern and fevered investigation. I definitely am not in my best mental state right now but I'm not freaking out either. However I am feeling low especially when I consider that I may have put myself in an irreversible situation, however remote that possibility may or may not be, which leads me to my desire to get as accurate of a picture of what's going on as I possibly can. I've definitely had an upset stomach and discomfort over this and for now am chalking it all up to hyper awareness of my body, like feeling itchy because you see someone else scratching I have no severe pains only slight discomforts. tl;dr 3.6cm liver lesion detected with CT scan with contrast declared most likely benign, ALT 79, and persistent palpitations with sustained elevated heart rate, no history of drug use or smoking (no vaping either), no stds. Apologies for the long submission and thank you for your time.
Hello, people. I'm 16, and I've had a chronic disease that's been on and off for the last 5-6 years. My gp is pretty clueless, as am I unfortunately, and after some back and forth from going into remission from having flares that spread out for months, I've been connected to a gastro enterologist who I've done a gastroscopy with, that turned out to be fruitless. (I do have some form of gastritis, but I don't have the report right now so I can't be sure which.) An upper abdominal MRI is planned in march, as well as an ultrasound to check my lymphs. I also had a CT last spring which showed adenomegaly, hepatomegaly, lumps in my colon and pelvis with a normal sized appendix, which was the goal of the scan. Also negative allergy and ANA blood tests, and my blood count shows relatively high calcium (2.51 mmol/L, 101 mg/L) and high bilirubine conjugates (3.3 mg/L and 5.6 micromol/L) as well as a number to do with the liver that's pretty low, idr which haha. The flares usually manifest as severe acid reflux, stomach cramps, shortness of breath, wheezing, coughing and fun stuff like that. I'm also seeing a psychologist because of the mental collateral damage this all has caused, from making me miss school and having to justify this to my family. Since the next appointment is still a bit more than a month away I was just looking for some guidance. Do you guys think this might be sarcoidosis? Is some of this ringing a bell? I'd love to hear from those who have gastrointestinal involvement, or just systemic in general, since it's also affecting my eyes, skin, muscles, nose, hair and joints in cool ways like hypersensitivity and stuff. If not, some ideas on other places to look would be appreciated. I will definitely ask for a rheumatologist appointment with my internist if he isn't convinced. Sorry for the formatting, I'm on mobile. I'm also dutch living in luxembourg, if that helps. Looking forward to hearing from you all.
Conjugated bilirubin literally off the charts! 70+ mg/dcl.
My father had a liver xplant two weeks ago and was literally signing papers to be transferred to an occupational therapy center after day 6. It's now day 13 and his conjugated bilirubin score is >70.4, higher than the instrument can even measure. The perplexing issue for the doctors is the enzymes and other liver numbers have remained within normal levels the entire time. Two endoscopy procedures of the biliary system were done and no obstructions were found. A biopsy was done from 2 locations, and the results showed a ”healthy liver." Potentially related issues: The doctors postulate the abnormal liver function is a result of infection. He has e coli sepsis and his latest white blood cell count had it's first drop from 40.6 to 26; encouraging. He is not on anti rejection because of the immuno suppression, of course. Interestingly, twice he's had unanticipated bleeding from surgeries. As a consequence, he's getting a lot of blood and I wonder if this is exasperating the high bilirubin issue as these extra red blood cells die. My father has obviously regressed to the point I'm not sure he makes it through the weekend. I need your help medical. You could very well save my dad...
Hi! So I was diagnosed with crohns about a year ago and have been on azathioprine since the summer. A lot of my GI problems are better managed now (my last scope showed that a good portion of my intestine has healed) but I still struggle with a few other symptoms. One is joint pain, but that comes and goes and often correlates to how my intestines are doing. The other is muscle fatigue and slight pain in my upper right abdomen. I got my blood work back today and say that my conjugated bilirubin levels are twice as high as they were in May (at .6) and was wondering if I should have someone look at my liver. Also, as far as the muscle weakness goes, there are days such as today where my hands are so weak and tingly that I have a hard time writing and taking notes in class. Does anyone else have experience like this??
Guess the illness! Symptoms inside. Will update with diagnosis.
Hi All, A patient (27, F, Caucasian, no children) complained of intense stomach pains and went to the clinic. Clinic found leukocytes in urine*, assumed UTI. Patient got sulpha-related medication for UTI. Later culture shows no UTI. Patient has itching of the extremities which proceeds into an entire body rash (hot, itchy). Patient then becomes jaundiced. Blood test shows very high bilirubin count, gets admitted to ER. Patient has ultrasound of the liver, no blockage of bile duct detected. Patient does not engage in high risk activities, however she spent 3 years living in Japan (came home August). The tests are still ongoing with her. Blood tests don't indicate an allergic reaction occurring. Both the liver cell levels and liver duct levels are high, but duct levels are slightly higher. Bilirubin has remained steady and elevated for the past four days. What do you guys think it is? The doctors at the hospital are all disagreeing with each other (internal medicine, auto-immune and allergy specialists are involved so far). If any of you guess it correctly, I'll update the original post with the winner. Brainstorm away! *previously wrote glucocytes, my apologies. EDIT: I am compiling all the answered questions into an edit of the OP for ease. -Hep tests are coming back today, I'll let you know. -Conjugated bilirubin is high -urine is dark yellow and foams bright yellow when shaken -Abdo exam came up with no pain or enlargement of liver -The rash originally resembled petechiae, then formed raised red plaques on the torso -PT was born with a poorly functioning kidney causing intense pains that were onset at puberty. 70% of kidney was surgically removed in 2003, PT no longer has pains. -Family history: PTs father had Sarcoidosis (of the lung), sister is allergic to sulfa I hope to have updates for you all very soon!
Interesting (relatively rare) case I saw last week
Hi Meddit! (I'm a medical student, so please forgive me if this case is not particularly challenging for many of you. Hopefully it'll at least be interesting!) Patient is a 25 year old woman from South Africa, who is HIV positive. She was diagnosed in 2010, and is currently on ARVs (TDF/FTC/EFV). Her most recent CD4 count is 112. She also had pulmonary TB in 2009, and completed her 6/12 of treatment. She was admitted to a tertiary hospital in the area earlier in the year because "[her] eyes were yellow, and [she] got bags of blood and yellow liquid." She received "pills" there for two months, but then defaulted further appointments. Now her primary complaint is of a week's duration of fatigue, decreased effort tolerance and dizziness. She has had no orthopnea/PND. She also reports a three day history of cough - non-productive, no haemoptysis, no pain, no recent night sweats/loss of weight/loss of appetite. There is also a curious episode of transient, complete right arm weakness, lasting ± 1 day. Her urine has also been red, for "a while". No history of epistaxis, menorrhagia, easy bruising, melaena, nausea/vomiting/diarrhoea. Non-smoker, non-drinker, no use of illegal drugs. No other medication. No family history of similar problems. On exam: HR 116 bpm, RR 38 br pm, BP 110/60, T 38 degrees, finger-prick Hb 6.8 g/dL, sats 99% on FMO2, 85% off O2. Normal finger-prick glucose. Very pale conjunctivae and oral mucosa. ?slightly jaundiced. Not oedematous, not clubbed, no lymphadenopathy. No obvious petechiae/purpura/ecchymoses. Resp tachypnoeic, but not distressed. Trachea central. Dullness to percussion right lower zone. Coarse crackles right lower zone, with decreased air entry. CVS tachycardic, but otherwise completely normal. Abdo soft, non-tender. No hepatosplenomegaly. Normal bowel sounds. CNS GCS 15/15, normal cranial nerve exam, normal motor and sensation exam, normal cerebellar exam. Dipstix 4+ blood, 2+ protein So what do you guys think? That's as much information we had going in to it :) What are your differential diagnoses, and which investigations would you like/need to include/exclude those diagnoses? I'll post updates with investigations as we go! Update 1 sorry for the delay; time zones are real, yo! CBC (or full blood count as we call it here) - we might use different units, so I'll just comment increased, decreased etc. Hb 6.7 WCC 7.99 (4-10) Platelets 7 (ultra low) MCV 104.5 (increased) MCH 34.0 (increased) MCHC 32.7 (normal) RCCount 1.97 (decreased) Hct 0.205 (decreased) RCDW 19.2 (increased) Smear: 10% fragments, polychromasia, mild toxic granulation D-dimer positive ECG normal (except for sinus tachy) CXR: left upper lobe shows extensive fibrosis, likely from previous TB right lower lobe and inferior upper lobe show opacification with air-bronchograms. Not a ground glass appearance. Sodium 137 Potassium 3.7 Urea 6.5 Creatinine 63 (all normal) So where does that leave everyone? Update 2 Fantastic theories coming through, everyone! Sorry I'm not updating at shorter intervals - just got back from call. One person has suggested the correct diagnosis so far. Here is another batch of test results: LFTs Bilirubin total 13 µmol/l (0 — 21) Bilirubin conjugated 5 µmol/l (0 — 6) Total Protein 98 g/l (60 — 85) Albumin 40 g/l (35 — 52) ALP 118 U/l (40 — 120) GGT 30 U/l (0 — 35) ALT 11 U/l (5 — 40) AST 31 U/l (5 — 40) LDH 982 (100-190) INR 1.04 PTT normal Fibrinogen normal Direct Coombs negative Haptoglobin < 0.20 (0.30-2.00) ANA negative Anti-dsDNA negative C3 and C4 normal So get your final differentials in - answers tomorrow! Hope everyone has enjoyed this so far. Update 3 Answer time! The patient's diagnosis was secondary TTP, likely associated with HIV. I think Chayoss was the first person to suggest it, so hats off to him/her. For everyone who was a bit thrown by respiratory involvement (as I was initially), Hickam's Dictum is a reminder that it's not always a single condition causing all the patient's symptoms/signs. In this case, she also had a CAP. She was transferred to our local tertiary hospital, where she apparently did very well. It turns out that she was known to them, and had been admitted with TTP in April this year. She had not returned for her follow up appointments after 2/12. Her biggest issue going forward is probably going to be her HIV management her CD4 is low and her viral load is high, despite nearly four years of ARV treatment. Her adherence has not been perfect, and there is concern that she may need to be switched our second line ART regimen (lopinaviritonavir, lamivudine, efavirenz). I hope this was a fun exercise. I saw another interesting (less uncommon) case the week before, so if anyone is keen I can put that one up as well. Have a good weekend, Meddit.
Is my dog going to be ok? My vet doesn't know what's wrong and I'm worried.
Species: Dog Age: 4 Sex/Neuter status: F/Spayed Breed: Pitbull Body weight: 55 lb History: She started acting lazy and tired. Her eating went down and she started drinking more. She developed fluid around her lungs, which the vet drained yesterday. Her liver and spleen are enlarged. Her Dad died of Immune Mediated Hemolytic Anemia. Clinical signs: See above Duration: 4 days Your general location: Chicago Illinois Links to test results, X-rays, vet reports etc: Hematology 11/7/17 (Order Received) 11/8/17 1:22 AM (Last Updated) TEST RESULT REFERENCE VALUE RBC 6.62 5.39 - 8.7 M/µL Hematocrit 48.4 38.3 - 56.5 % Hemoglobin 16.3 13.4 - 20.7 g/dL MCV 73 59 - 76 fL MCH 24.6 21.9 - 26.1 pg MCHC 33.7 32.6 - 39.2 g/dL % Reticulocyte 2.1 % Reticulocyte 139 10 - 110 K/µL H Reticulocyte Comment In nonanemic dogs, a reticulocyte count of greater than 110 K/uL of blood may be a transient physiologic response or evidence of bone marrow response to an increased peripheral demand. A persistent reticulocyte count >110 K/uL may indicate occult blood loss, underlying hemolytic disease or disorder that causes an absolute erythrocytosis. Serial monitoring of the erythrogram and reticulocyte count may help determine the significance of this finding. The following chart can be used as a guideline to determine the degree of regenerative response. Degree of bone marrow response (K/uL): Mild 110-150 Moderate 150-300 Marked >300 WBC 13.2 4.9 - 17.6 K/µL % Neutrophil 78.6 % % Lymphocyte 11.0 % % Monocyte 4.5 % % Eosinophil 5.8 % % Basophil 0.1 % Neutrophil 10.375 2.94 - 12.67 K/µL Lymphocyte 1.452 1.06 - 4.95 K/µL Monocyte 0.594 0.13 - 1.15 K/µL Eosinophil 0.766 0.07 - 1.49 K/µL Basophil a 0.013 0 - 0.1 K/µL Generated by VetConnect® PLUS November 8, 2017 09:54 AM Page 1 of 4 MUSE PET OWNER: DATE OF RESULT: 11/7/17 LAB ID: 1900844177 Hematology (continued) TEST RESULT REFERENCE VALUE Platelet 420 143 - 448 K/µL a AUTOMATED CBC Chemistry 11/7/17 (Order Received) 11/8/17 1:22 AM (Last Updated) TEST RESULT REFERENCE VALUE Glucose 103 63 - 114 mg/dL IDEXX SDMA a 13 0 - 14 µg/dL Creatinine 1.1 0.5 - 1.5 mg/dL BUN 14 9 - 31 mg/dL BUN:Creatinine Ratio 12.7 Phosphorus 5.7 2.5 - 6.1 mg/dL Calcium 11.2 8.4 - 11.8 mg/dL Sodium 147 142 - 152 mmol/L Potassium 5.1 4.0 - 5.4 mmol/L Na:K Ratio 29 28 - 37 Chloride 109 108 - 119 mmol/L TCO2 (Bicarbonate) 25 13 - 27 mmol/L Anion Gap 18 11 - 26 mmol/L Total Protein 6.0 5.5 - 7.5 g/dL Albumin 3.0 2.7 - 3.9 g/dL Globulin 3.0 2.4 - 4.0 g/dL Alb:Glob Ratio 1.0 0.7 - 1.5 ALT 195 18 - 121 U/L H AST 101 16 - 55 U/L H ALP 68 5 - 160 U/L GGT 6 0 - 13 U/L Bilirubin - Total 0.3 0.0 - 0.3 mg/dL Bilirubin - Unconjugated 0.2 0.0 - 0.2 mg/dL Generated by VetConnect® PLUS November 8, 2017 09:54 AM Page 2 of 4 MUSE PET OWNER: DATE OF RESULT: 11/7/17 LAB ID: 1900844177 Chemistry (continued) TEST RESULT REFERENCE VALUE Bilirubin - Conjugated 0.1 0.0 - 0.1 mg/dL Cholesterol 157 131 - 345 mg/dL Creatine Kinase 251 10 - 200 U/L H Hemolysis Index N b Lipemia Index N c a BOTH SDMA AND CREATININE ARE WITHIN THE REFERENCE INTERVAL which indicates kidney function is likely good. Evaluate a complete urinalysis and confirm there is no other evidence of kidney disease. b Index of N, 1+, 2+ exhibits no significant effect on chemistry values. c Index of N, 1+, 2+ exhibits no significant effect on chemistry values. Urinalysis 11/7/17 (Order Received) 11/8/17 1:22 AM (Last Updated) TEST RESULT REFERENCE VALUE Collection FREE-CATCH Color DARK YELLOW Clarity CLOUDY Specific Gravity 1.030 pH 5.0 Urine Protein 1+ (100-200 mg/dL) a Glucose NEGATIVE Ketones TRACE b Blood / NEGATIVE Hemoglobin Bilirubin 1+ Urobilinogen NORMAL White Blood 2-5 Cells 0 - 5 HPF Generated by VetConnect® PLUS November 8, 2017 09:54 AM Page 3 of 4 MUSE PET OWNER: DATE OF RESULT: 11/7/17 LAB ID: 1900844177 Urinalysis (continued) TEST RESULT REFERENCE VALUE Red Blood Cells 0-2 HPF Bacteria NONE SEEN Epithelial Cells RARE (0-1) Mucus NONE SEEN Casts NONE SEEN Crystals 2+ CALCIUM OXALATE DIHYDRATE (6-20)/HPF a Protein test is performed and confirmed by the sulfosalicylic acid test. b Detection of trace ketones in patients who are normoglycemic or have negative urine glucose is non-specific and of limited clinical significance. Endocrinology 11/7/17 (Order Received) 11/8/17 1:22 AM (Last Updated) TEST RESULT REFERENCE VALUE Total T4 a 1.7 1 - 4 µg/dL a Interpretive ranges: <1.0 Low 1.0-4.0 Normal
Hello everyone, this will by my last big post for a little while. I wanted to address hepatotoxicity since it seems to be this big grey area for a lot of people. Drug metabolism is a very complicated processes, so I have tried to condense it into a readable format. I wanted to address how drugs are metabolized, how drug metabolism can affect the liver, how to determine liver damage, and how to prevent it. Please feel free to ask questions! Drug Metabolism When it comes to drug metabolism, the liver’s primary function is to metabolize the drug into a form that is suitable for elimination by the kidneys. The main goals of this metabolism is to reduce fat solubility, make the drug water soluble, and to decrease its biological activity so that it stops working. This occurs for not only foreign substances (known as xenobiotics, which drugs are considered), but also endogenous chemicals. Drug metabolism in the liver exists in two main phases, phase I and phase II.
Phase I: Phase I metabolism happens primarily in the smooth endoplasmic reticulum of hepatocytes. The main purpose of this phase is to make lipid soluble compounds water soluble. This typically renders the metabolites of the drug to be inactive, but not always.
Phase II: Phase II metabolism takes place in the cytosol of hepatocytes. In this phase, the products from phase I will undergo conjugation to increase their water solubility.
The efficacy of the enzymes used in drug metabolism are age-dependent. In newborns and the geriatric, the ability to metabolize drugs is greatly decreased. Smoking can increase the efficacy of drug metabolism through the inhalation of polycyclic aromatic hydrocarbons. This is most noticeably manifested in the increased metabolic activity of caffeine. Drug Induced Hepatotoxicity Drug induced hepatotoxicity can have many causes. Some medications cause direct damage to hepatocytes while others block certain metabolic processes. As an example, acetaminophen itself is not the source of hepatotoxicity, but rather one of its metabolites. When taken in extreme quantities, this metabolite accumulates because the enzymes required are unable to keep up in phase II metabolism and cell damage occurs. Likewise, mitochondrial damage can increase oxidative stress which can damage hepatocytes. These causes are categorized in seven general categories based on the mechanism of hepatotoxicity. The main categories where AAS and ancillaries are implicated are:
Steatosis: Steatosis is the accumulation of triglycerides in the liver. Liver function tests (LFTs) are unreliable when it comes to the diagnosis of hepatic steatosis. Often will have an AST/ALT ratio < 1. Imaging and possible biopsy is required to make an accurate diagnosis. AST and ALT both upwards of 4 times ULN. Tamoxifen and raloxifene have been shown to induce hepatic steatosis.
Zonal Necrosis: Zonal necrosis is essentially the death of cells in a specific zone of the liver. This is the most common manifestation of hepatotoxicity. This will cause an increase in ALT with normal ALP levels. This can be caused by C-17-alpha-alkylated (C17aa) steroids.
Cholestasis: Cholestasis is the impediment of biliary flow from the liver through the biliary tract. This is the cause of jaundice. The increase in bilirubin causes a yellowing of the skin and that is occurs with itching. C17aa steroids may cause hepatotoxic cholestasis. This can be seen on labs as normal levels of ALT and > 2 times ULN ALP. The mechanism of this is not well known. Testosterone and 19-nortestosterone compounds have been implicated in cases of hyperbilirubinemia, but rarely to the point of jaundice.
Hyperplasia and Neoplasia: C17aa compounds have been implicated in cases of hepatic hyperplasia and neoplasia, essentially cancer. However, non-C17aa steroids have also been noted as a cause of liver cancer in medical case reports.
Vascular Lesions: These vascular lesions are known as Peliosis Hepatis. These lesions are present on endothelial cells of hepatic vasculature and is typically asymptomatic. This can eventually lead to hepatomegaly (enlarged liver) and frequently death if untreated.
Effects of liver damage include jaundice, ankle edema, gynecomastia, increased bleeding due to decrease in clotting factor synthesis. Most of these effects come from deficiencies in synthesis of their respective plasma proteins. For example, damage to hepatocytes that are responsible for synthesis of SHBG will result in a decrease in SHBG. This will alter the free estrogen/free androgen ratio, potentially inducing gynecomasta. Likewise, a decrease in plasma proteins will change the blood colloid osmotic pressure, causing a change in capillary net filtration pressure leading to edema in the lower extremities. Liver Function Tests LFTs can be done to assess hepatic function. These are not exactly conclusive and require some sort of follow up to assess the degree of severity. Often this will be some sort of imaging or biopsy. Most of these biomarkers are assessed in a multiplication of the upper limit of normal (ULN), which is the top end of the normal range. Aminotransferases: Aminotransferases are enzymes that are used in the synthesis of amino acids. There are two aminotransferases that are checked as part of an LFT.
Aspartate Transaminase (AST): Reference range: 8 - 40 IU/L. While AST is found in the liver, this enzyme is also found in great quantities in cardiac and skeletal muscle. Because of these other sources, AST alone is not a good indicator of liver damage. Essentially, AST does not require the entire cell to be damaged for it to enter the plasma, where ALT does. This is due to its location within the cell. If AST is elevated then there is a good possibility that the source of the AST is from muscle damage. This can be caused by myocardial infarction (heart attack), rhadomyolysis, and even resistance training. This is why slightly elevated AST levels should not be of concern if you lift frequently.
Alanine Transaminase (ALT): Reference range: ≤ 52 IU/L. Much like AST, ALT is an enzyme used to catalyze the synthesis of amino acids. Unlike AST, ALT is found predominantly in the liver and requires significant damage to hepatocytes for it to be released in to the plasma.
AST to Platelet Ratio Index (APRI): This typically won’t be included in lab tests, but it is easy to figure out. An online calculator can be found here. APRI has been shown to be a predictor of liver cirrhosis. Alkaline Phosphatase (ALP): Reference rage: 30 - 120 IU/L. ALP is an enzyme that is located within hepatic biliary ducts. Elevations in plasma concentrations of this enzyme are indicative of either cholestasis or biliary obstruction. In these pathologies, ALT and AST may remain unaffected. Total Bilirubin: Reference range: 0.1-1.0 mg/dL. Bilirubin is a byproduct of hemoglobin catabolism. The heme group of hemoglobin is broken down into biliverdin, then bilirubin, which is transported to the liver for the production of bile salts along with urobilin (the pigment that makes urine yellow) and stercobilin (the pigment that makes feces brown). High hepatic sources of bilirubin are indicative of cirrhosis or hepatitis. 5'-nucleotidase (5'NTD): Another biomarker used int he diagnosis of cholestasis. Liver Protection
Cessation: Hepatotoxic drug withdrawal is the widely accepted treatment for drug induced liver damage.
Tauroursodeoxycholate (TUDCA): TUDCA is a bile acid that was found in bears. It is currently being researched in the treatment of ophthalmologic and neurologic conditions. TUDCA has been shown to reduce cholestasis, hepatic steatosis, cirrhosis, and transient liver enzyme levels. The extent of this efficacy still needs more research and clinical trials. No research exists to support its use in zonal necrosis, peliosis hepatis, or hyperplasia.
Milk Thistle: This is bullshit, don't waste your money
I have been doing keto since last August, starting lazy, then strict and again doing lazier keto. Here is the result (conversion used), I have inserted a "+" where the result was higher than the recommended limit: A1C : 4,17% Triglycerides: 0.73 mmol/l, 13 mg/ dl AST (GOT): 30 ALT (GPT): 23 GGT: 13.60 u/l ALP: 148 u/l +Total cholesterol: 5.91 mmol/l ; 105 mg/dl + LDL: 3.8 mmol/l or 68 mg/dl HDL: 1.78 mmol/l or 33 mg/ dl Sodium: 140 mmol/l or Mg: 0.91 mmol/ l or 17 mg/ dl Potassium: 4.2 mmol/l or 76 mg/ dl Vitamin D: 86.3 nmol/l or 24.9 ng/ml +Total bilirubin: 36.6 umol/l or 2.14 mg/ dl +Conjugated bilirubin 7 umol/l or 0.4 mg/ dl As you can see, LDL, total cholesterol and especially the bilirubin levels are high. Should I be concerned? Any input would be appreciated. I will get the test repeated in 3 months time. Is there anything else that should be added to it?
What I don't understand is how non functional or a malfunction of UDPglucuronosyltransferase affects this type of treatment. Also, does this apply to Gilbert's syndrome These considerations demonstrate the need for alternative treatment strategies. Most hypobilirubinemic treatments, as described in chapters 1 and 2, stimulate the fecal excretion of bilirubin via the bile. Biliary bilirubin excretion, however, is highly inefficient in patients with Crigler-Najjar disease and, to a lesser extent, in patients with neonatal jaundice. This is due to an inactivated (Crigler-Najjar disease) or immature (neonatal jaundice) isoform of the enzyme UDPglucuronosyltransferase. This hepatic enzyme catalyzes the transfer of glucuronic acid to bilirubin, thus forming bilirubin monoglucuronoside or diglucuronoside. This so-called conjugated bilirubin is more water soluble, and can readily be excreted into the bile. Bilirubin, however, is not exclusively excreted via the bile, but may also enter the intestinal lumen via direct transmucosal excretion from the blood. The efficiency of this excretory pathway is decreased, however, by reabsorption of unconjugated bilirubin from the intestinal lumen. This reabsorption can be prevented by intestinal capture; the binding of intestinal unconjugated bilirubin to orally administered agents.
Been using 100-200mg/day for 3-4 weeks then got a liver test... Results came back normal! Tianeptine does not seem likely to cause liver damage, even in medium-high doses (granted your liver is normal/healthy and so is the way your body metabolizes this drug). Just keep in mind there's probably a small chance whatever you are buying off the internet is not in fact Tianeptine or it might be cut (who knows). Also keep in mind, that some samples (especially if you buy straight powder that isn't branded) may have trace amounts of arsenic and lead, but probably not enough to cause health issues...
Hepatic Funct Panel Collected:3/31/2016 11:11 AM Status: Final result Normal Ref Range 7d ago Total Protein (6.1-8.2 g/dL) 6.9 Albumin (3.9-5.0 g/dL) 4.5 Bilirubin,Total (0.1-1.2 mg/dL) 0.3 Bilirubin,Conjugated (<=0.3 mg/dL) <0.2 Alkaline Phosphatase (37-113 U/L) 73 Aspartate Aminotransferase (13-47 U/L) 21 Alanine Aminotransferase (8-64 U/L) 17 Specimen Collected:03/31/16 11:11 AM Last Resulted:03/31/16 1:32 PM
All of these values fall within the normal range (normal range as shown in the parenthesis). Better yet, I urine drug tested myself and Tianeptine does not come back positive for TCA's or opiates! If you don't believe me, maybe i'll post the pics to prove it. Possibly I'm jumping the gun here and might need to take another liver function test further down the road, but so far so good! No side effects and has worked wonders for my motivation and depression! I split my doses into 2 or 3 a day. Something like 70-100mg in the morning and 40-80mg in the evening and haven't had any problems with tolerance yet as it's still effective. I do however find it hard to get going in the morning until I've had my morning dose and have waited 30 minutes for it to kick in... The short half-life sucks.
[University Clinical Chemistry] Jaundice, Bilirubin, and Urobilinogen
I'm having a bit of trouble trying to figure out this question. A patient is admitted to the hospital. Urinalysis and chemistry results are given. Urinalysis results: Nothing noteworthy except for 3+ positive for bilirubin, amber appearance, and normal urobilinogen (3umol/L). Chemistry results: Total bilirubin, direct bilirubin, AST, ALT, ALP, and GGT are all elevated (high). T.Bil: 47 umol/L D.Bil: 40 umol/L ALP: 535 U/L AST: 90 U/L ALT: 97 U/L GGT: 415 U/L Total Protein (65 g/L) and Albumin (48 g/L) results are normal. The question asks what type of jaundice this patient has, list several conditions that can cause it, and also asks why the urine urobilinogen result is normal. Based on the AST, ALP, ALT, and GGT results I believe this is post-hepatic jaundice and I've listed several conditions relating to it. The problem is I have no idea why the urine urobilinogen would be normal. From my understanding if the biliary system is obstructed, then there will be decreased amounts of conjugated bilirubin traveling from the liver to the intestine where it will be converted to urobilinogen, which some of it will be excreted from the kidneys. Would there not be decreased urobilinogen instead?
[Science] Gilbert’s Syndrome Successfully Treated with the Paleolithic Ketogenic Diet
Abstract Gilbert’s syndrome (GS) is a common hyperbilirubinaemia syndrome caused by reduced conjugation of serum bilirubin by the liver. Although it is considered as a common and harmless condition not requiring treatment symptoms associated with GS may be unfavorable. Here we present a case of GS where high level of total and direct bilirubin, yellowish discoloration of the sclera as well as associated symptoms including migraine, fatigue and granulomatosus dermatitis were reversed following a shift toward the popular paleolithic and then toward the paleolithic ketogenic diet.
Elevated conjugated bilirubin should lead to increased total bilirubin. If the patient has normal conjugated bilirubin levels and elevated indirect bilirubin levels, it is a sign either of excessive hemolysis or of a failure of the liver as it struggles to cope with the normal rate of hemolysis. The level of direct, indirect and total bilirubin will be measured as part of a standard liver panel test. Direct bilirubin 7.5 mg/dl high, indirect bilirubin normal 0.6 mg/dl. Direct bilirubin 11.0 mg/dl high, indirect bilirubin slightly elevated 0.9 mg/dl. 3. Both conjugated and unconjugated bilirubin are elevated, values are almost the same, commonly results from hepatic diseases, for instance: Direct bilirubin 9.0 mg/dl, indirect bilirubin 8.0 ... Bilirubin is a yellowish substance in your blood. It forms after red blood cells break down, and it travels through your liver, gallbladder, and digestive tract before being excreted. Typically,... Conjugated bilirubin (direct bilirubin) —formed in the liver when sugars are attached (conjugated) to bilirubin. It enters the bile and passes from the liver to the small intestines and is eventually eliminated in the stool. Normally, no conjugated bilirubin is present in the blood. Figure 1. Unconjugated bilirubin and conjugated bilirubin metabolism Conjugated or direct hyperbilirubinaemia occurs when the the liver is able to conjugate bilirubin, but the excretion is impaired. Causes include: failure of bilirubin excretion by hepatocytes: Dubin-Johnson syndrome; Rotor's syndrome; obstruction to biliary flow i.e. cholestasis, both intra-hepatic and extra-hepatic The conjugated (direct) bilirubin level is often elevated by alcohol, infectious hepatitis, drug reactions, and autoimmune disorders. Posthepatic disorders also can cause conjugated hyperbilirubinemia. Bilirubin is formed by a breakdown product of heme rings, usually from metabolized red blood cells. Click to see complete answer. Englisch: conjugated bilirubin, direct bilirubin. Inhaltsverzeichnis. 1 Definition; 2 Labormedizin. 2.1 Material; 2.2 Normwert; 2.3 Interpretation; 2.4 Hinweise; 3 Literatur; 1 Definition. Das direkte Bilirubin ist die wasserlösliche Form des Bilirubins. Durch das Enzym UDP-Glucuronosyltransferase wird in der Leber Glucuronsäure an Bilirubin konjugiert, es entsteht konjugiertes Bilirubin ... A high level of bilirubin in the blood is known as hyperbilirubinemia. High bilirubin levels can cause jaundice. Jaundice makes the skin and the whites of the eyes appear yellow, due to the brown... Most of this conjugated bilirubin goes into the bile and out into the small intestine. (An interesting aside: some of the conjugated bilirubin remains in the large intestine and is metabolized into urobilinogen, then sterobilinogen, which gives the feces its brown color! Now you know.) So: if you have an increase in serum bilirubin, it could be either because you’re making too much bilirubin ... We used a system capable of measuring conjugated bilirubin and its monoconjugated and diconjugated fractions in serum to assess bilirubin conjugation in 29 glucose-6-phosphate dehydrogenase (G6PD)-deficient, term, male newborn infants and 35 control subjects; all had serum bilirubin levels > or = 256 mumol/L (15 mg/dI). The median value for diconjugated bilirubin was lower in the G6PD ...
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