Conjugated bilirubin as a reflex test for increased total

Aims: This study aimed at examining the oxidative stress level of sickle cell anaemia subjects using glutathione and bilirubin levels as markers as well as the red cell parameters.
Study Design: Case-control study.
Place and Duration of Study: University of Calabar Teaching Hospital, Calabar-Nigeria, between August 2018 and July 2019.
Methodology: Subjects comprised 45 SCA patients (27 females, 18 males; age range 10-45 years) attending clinic at University of Calabar Teaching Hospital Calabar, Nigeria and equal number of age and sex-matched control subjects with Hb AA. Blood samples were collected and analyzed by standard methods. The red cell parameters were analysed by automation using FY-Smart-1 auto haematology analyzer. Bilirubin assay was performed using the colorimetric method, while glutathione was performed by enzyme-linked immunosorbent assay technique.
Results: The red blood cell count, haemoglobin concentration, and haematocrit values of SCA subjects were significantly lower (p=0.001) compared to values from control subjects, while the red cell indices and red cell distribution width values were increased in SCA subjects (p=0.001). The Total bilirubin, conjugated bilirubin and unconjugated bilirubin were significantly increased (p=0.001) among SCA subjects, while the glutathione concentration values were reduced (p=0.001) when compared to values obtained from control subjects.
Conclusion: SCA subjects have marked red cell size variation, lymphocytosis and thrombocytosis. The haemolytic events that occur in sickle cell anaemia results in glutathione depletion.
Please read full article : - www.journalibrr.com

I was diagnosed with Gilbert's Syndrome when I was 18. It is rare enough that I was on my 4th opinion before I was diagnosed. (The first 3 doctor's diagnoses were: faking it, hidden drug abuse, and faking it.)
Symptoms are: *Frequently Reported: fatigue, tiredness, brain fog, headaches, poor memory, dizziness, depression, irritability, anxiety, nausea, loss of appetite, irritable bowel syndrome (IBS), stomach pain & cramping, livegallbladder pain, abdominal pain, tremors, itchiness, jaundice
Commonly Reported: insomnia, difficulty concentrating, panic attacks, hypoglycemic reaction to foods, intolerance to carbs, food intolerances, alcohol intolerance, loose stools / diarrhea, abdominal bloating or swelling, breathlessness or labored breathing, heart palpitations, aching muscles / body ache, joint pain, numbness & tingling, weakness, chemical sensitivity, weight loss, lump in the throat, feeling constantly sick
Sometimes Reported: difficulty finding the right words, feeling drunk, vomiting, intolerance to fatty foods, strong hangovers, acid reflux, excessive thirst, chest pain, muscle twitches, cold hands and feet, environmental allergies, swollen lymph nodes, toxic feeling, bitter or metallic taste in the mouth, eye pain
Occasionally Reported: waking panic attack, mood swings, feeling antisocial, intolerance to drugs, constipation, pale stools, indigestion, back pain, dry skin, feeling cold, low body temperature, pale skin, low weight, night sweats, excessive sweating, poor immune system, sore or dry throat, light sensitivity, bloodshot eyes*
I have ALL of the above at one point or another in my life with the most common one being fatigue and irritability (and that was BEFORE going to law school).
*Elevated bilirubin levels are not enough to diagnose GS. The two primary reasons they can be elevated are from liver problems or blood problems (as in anemia, where too much bilirubin is produced). There are genetic tests for Gilbert's Syndrome, but it might be hard to get covered by insurance.
The best route is to be tested for liver problems, blood problems, and bilirubin levels. The liver test is called a 'liver function test'. For the bilirubin test, have your total bilirubin, conjugated bilirubin, and unconjugated bilirubin levels tested. When total bilirubin is elevated, unconjugated bilirubin is making up a large majority of your total bilirubin count, and no other liver or blood problems are apparent, Gilbert's Syndrome is properly diagnosed.*
I am now in my late 30's, training for a half marathon and have figured out some ways to stay ahead of the symptoms.

1. I stopped eating meat, I only occasionally eat fish. The fat content was really exacerbating a lot of the symptoms, especially the lethargy.
   
2. Really (trying like hell) to cut back on sugar, especially soft drinks and baked goods.
   

If anyone else has this or has questions, please let me know with a response or PM.
For more info check out http://www.gilbertssyndrome.com/

Can conjugated bilirubin form gallstones? Usmle RX says "conjugated bilirubin is water soluble and therefore does not form stones".
I thought if a patient had a lot of hemolysis going on for example, their spleen would send lots of unconjugated bilirubin to the blood/liver, then the liver would conjugate that huge amount of UCB and then bile would be supersaturated with conjugated bilirubin, leading to pigment gallstones formation. If a functional liver adds COnjugated bilirubin into bile, how could UCB be secreted into bile?
What do you guys think? Thanks in advance.

This concept has always confused me I would appreciate any clarification please:
Unconjugated bilirubin from heme breakdown gets carried by albumin and goes to the liver where it gets conjugated and excreted in bile. Why is it even getting conjugated it it’s going to get deconjugated in the gut to form urobilinogen? :/

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).
  • https://books.google.com/books?id=hfwlDwAAQBAJ&pg=PA108#v=onepage&q&f=false
  • https://books.google.com/books?id=dwMyBwAAQBAJ&pg=PA513#v=onepage&q&f=false

In short: Oral Steroid (active) -> Hepatic Breakdown -> Metabolite (inactive)

• [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.

• https://pubmed.ncbi.nlm.nih.gov/27372877/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772995/
• https://www.researchgate.net/publication/303806187_Anabolic_androgenic_steroid-induced_hepatotoxicity
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC500485/

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
  • https://www.ncbi.nlm.nih.gov/books/NBK548902/
  • https://www.ncbi.nlm.nih.gov/books/NBK548475/

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.

• https://www.ncbi.nlm.nih.gov/books/NBK482279/

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.
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967529/#:~:text=In%20addition%20to%20its%20antioxidant,induced%20vasodilation%20(Millea%202009)).

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.

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270338/
• https://www.ncbi.nlm.nih.gov/books/NBK548401/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691167/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241507/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974141/

​
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

Sources

• - https://pubmed.ncbi.nlm.nih.gov/26892516/
• - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126306/
• - https://pubmed.ncbi.nlm.nih.gov/15486293/
• - https://pubmed.ncbi.nlm.nih.gov/24891994/
• - https://pubmed.ncbi.nlm.nih.gov/17559149/
• - https://pubmed.ncbi.nlm.nih.gov/11515630/
• - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC125009/?tool=pubmed
• - https://pubmed.ncbi.nlm.nih.gov/9918905/
• - https://pubmed.ncbi.nlm.nih.gov/9146783/
• - https://pubmed.ncbi.nlm.nih.gov/18436848/
• - https://pubmed.ncbi.nlm.nih.gov/8674405/

​
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.”

• https://pubmed.ncbi.nlm.nih.gov/16194047/

“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.”

• https://pubmed.ncbi.nlm.nih.gov/2065700/

“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.”

• https://pubmed.ncbi.nlm.nih.gov/8279671/

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.”

• https://pubmed.ncbi.nlm.nih.gov/12499076/

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 that may improve liver function and exhibit hepatoprotective effects. IT SHOULD IN NO WAY YOUR ONLY LIVER SUPPORT MEDICATION, but there is nothing wrong with using it.

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.

Cat is domestic shorthair, fixed.
Cat was overweight (c. 12-13 pounds) and lost a large amount of weight in about six weeks (now 7-8 pounds). She went to the vet to get blood tested Wednesday when she seemed to have stopped/radically slowed her eating. (Detection of this was not great because another cat was sneaking in and eating her food.) She was somewhat lethargic and occasionally distressed when we made the appointment the week before, and not doing better when she went win. Blood results are below.
She was in acute distress that evening (vomiting foam repeatedly, making unhappy noises, walking in a crouch with her head to the side). I do not think the vet visit caused this; she was in some distress before. She spent two days at the vet still not eating much, and I came home with mirtazapine, which she got this morning. She was stressed and hostile to the vet staff, having enough energy to draw more blood from them than they from her.
Today, the cat will lick food but not eat. She is currently on my desk alternating between affection and annoyance. She is low-energy, but not in acute distress. She seems significantly more alert than she was before going to the vet.
Hmm, looks like images will be an issue. Typing!
Outliers:
ALT 1015
AST 274
ALP 189
GGT 7
Bilirubin, total: 1.5
Bilirupin, unconjugated: 0.6
Bilirubin, conjugated: 0.9
BUN:14
All other numbers normal. Glucose is 161.
Urine appears normal. Under Crystals is says: 1+bilirubin(1-5)/HPF
Other: Lipid droplets present.
Negative for cancers.
(Testing was by IDEXX.)
Appearance is solid at the rib cage, very very thin in the stomach and spine is just below skin. No discolorations or other anomalies.
She got a scan of some sort that showed no anomalies.
Any help would be appreciated.

Anking card says “hemolysis is associated with dark urine due to increased urine urobilinogen”
The extra section says “NOT due to increased unconjugated bilirubin, which is not soluble in water and thus absent in urine”
...this implies that the unconjugated bilirubin (from hemolysis) is conjugated somewhere along the away, since only conjugated bilirubin can be made into urobilinogen. Conjugation only happens in the liver, so is the urine dark bc the excess unconjugated bilirubin is traveling to the liver, where it becomes conjugated, which gets converted to urobilinogen by gut microbiota and then urobilin builds up in urine? Just confused how unconjugated bilirubin that’s been leaked out of RBCs would travel to the liver if it’s not soluble in plasma/water
Also can’t hemoglobinuria also be a cause of dark urine due to hemolysis bc of all the free hemoglobin released from RBCs?

Species: Feline Age: 3,5 years Sex/Neuter status: Male, neutered Body weight: 7.5 kg (16.5 lb) Clinical signs: frequent urination, thirst, general weakness. Duration: 5 days Your general location: Uruguay
On Tuesday he started to urinate a lot of times but a small amount. I counted 9 times in 2 hours. One of the times the urine was slightly red, when I showed it to the vet she said it was blood. This vet diagnosed him with oliguria and started a treatment with antibiotics and diuretic. The next day they made him an ultrasound which the results are: Both kidneys with pathology and echogenicity compatible with pyelocaliceal dilation and mild hydronephrosis.
When my cat showed the first symptoms he was eating and playing normally. But after I took him to the vet he was pretty bad. He wouldn't eat his regular dry food, only a little bit of wet food and was lethargic. That was very dangerous because in the ultrasound they saw that he has a principle of fatty liver so it could end in a liver lipidosis. So I took him to another vet where they made him urine and blood tests. The urine test was normal (so, no antibiotics prescription). They gave him fluid therapy (Fluid + B1 + B12) and Liver protection (Hepvet vitamin complex) in the clinic.
The other tests results were ready today:
Liver function:

Test	Res	Refs.
Total Bilirrubin	0.68	<= 1.0
Conjugated Bilirrubin	0.13	<= 0.3
Unconjugated Bilirubin	0.55	<= 0.6
Total Proteins	9.1	5.5 to 7.6
Albumin	2.9	2.5 to 3.5
Globulins	6.2	3.0 to 4.0
Alb/Glob	0.4	0.5 to 1.2
GPT/ALT	53	10 to 60
GOT/AST	22	10 to 60
ALP	136	<= 100
GGT	1.68	<= 10
Tot. Cholesterol	148	70 to 200

Hemogram:

Test	Res	Refs.
Red Blood cells	9.50	5 to 10
Hemoglobin	15.8	8 to 15
Hematocrit	42	24 to 45
MCV	44	40 to 55
MCH	16	13 to 17
MCHC	38	30 to 35
Platelets	110	150 to 600
leukocytes	18.1	5.5 to 19.5

Detailed White cell count:

Absolute Values	Res	Refs.
Neutrophiles	14.8	3 to 12.5
Lymphocyte	2.7	1.5 to 7
Monocytes	0.2	<= 0.5
Eosinophiles	0.4	0.1 to 1
Basophiles	0.0	0 to 10

Relative Values	Res	Refs.
Neutrophiles	82	35 to 75
Lymphocyte	15	20 to 55
Monocytes	1	1 to 4
Eosinophiles	2	2 to 7
Basophiles	0	0 to 0

Urea, creatinine, Phosphatemia

Test	Res	Refs.
Urea	0.79	0.15 to 0.60
Creatinine	2.01	0.70 to 1.80
Phosphatemia	3.37	3.0 to 6.5

They diagnosed a nephropathy. They told me that probably like 75% of his kidneys are not working anymore (which seems a quite arbitrary number to me) and that most cases like this end in a kidney failure. Is there a way for the nephrones to recover? If its correct that only a 25% of his kidneys are working, which is the prognosis? Will he be in pain?
Is there some way to treat this condition besides dieting? Now he is eating Hill's k/d (dry) and Hepvet. I know that wet food is better but it is impossible considering my location.
I'm looking for general advice and a fresh opinion. Sorry for my english. Thank you.

Anking card says “hemolysis is associated with dark urine due to increased urine urobilinogen”
The extra section says “NOT due to increased unconjugated bilirubin, which is not soluble in water and thus absent in urine”
...this implies that the unconjugated bilirubin (from hemolysis) is conjugated somewhere along the away, since only conjugated bilirubin can be made into urobilinogen. Conjugation only happens in the liver, so is the urine dark bc the excess unconjugated bilirubin is traveling to the liver, where it becomes conjugated, which gets converted to urobilinogen by gut microbiota and then urobilin builds up in urine? Just confused how unconjugated bilirubin that’s been leaked out of RBCs would travel to the liver if it’s not soluble in plasma/water
Also can’t hemoglobinuria also be a cause of dark urine due to hemolysis bc of all the free hemoglobin released from RBCs?

Zanki has a card :
Viral hepatitis is associated with dark urine due to increased urine {{c1::conjugated bilirubin}}
{{c2::Hemolysis}} is associated with dark urine due to increased urine {{c1::urobilinogen}}
So my understanding for hemolysis is that the dark urine is from increased unconjugated bilirubin that eventually gets converted to conjugated bilrubin and then urobilinogen. So would it also be correct to say viral hepatitis is associated with dark urine because of increased urobilinogen too? Like does the conjugated bilirubin get converted to urobilinogen in viral hepatitis?

Hey all! I'm currently learning all about RBCs, and we're currently reading the chapter about Hgb. I just wanted to make sure I had my flowcharts right, as my lecturer's slides have two flowcharts for each and I'm getting confused!

• Extravascular Destruction of Hgb
  • Inside the macrophage, Hgb is broken down into

1. Heme
   1. Broken down into CO (expired in the lungs) and Biliverdin.
   2. Biliverdin is reduced to unconjugated Bilirubin, which is then taken to the liver.
   3. Bilirubin is now conjugated and taken to the intestines, where the intestinal flora converts it to Urobilinogen.
   4. Urobilinogen can either be reabsorbed into the plasma and excreted in the urine, or excreted in stool as oxidized urobilin or stercobilin.
2. Iron
   1. It is stored as either ferritin or hemosiderin. Either is released to transferrin.
   2. Ferritin/hemosiderin is transported via transferrin to developing RBCs in the BM.
3. Globin
   1. Broken down into its constituent amino acids and recycled into the amino acid pool.

• Intravascular Destruction of Hgb (the pathway I'm most confused about.)
  • Hgb is released into the peripheral circulation, where it can

1. Dissociate into alpha and beta dimers, which then bind to Haptoglobin, forming a Haptoglobin-Hemoglobin complex. Due to the large size, the HpHb complex can not be filtered by the kidney.
   1. The dimers get carried to the liver.
   2. HpHb is taken up by Hepatocytes.
   3. Both undergo destruction similar to extravascular
2. Dissociate into alpha and beta dimers, but Hp is depleted.
   1. Alpha and Beta dimers are filtered by the kidneys and reabsorbed into proximal tubules, or...
   2. If levels exceed the renal threshold, they are excreted in the urine.
   3. Some iron will remain as hemosiderin and when renal cells slough off, hemosiderinuria forms (probably not the correct word but I'm brainfarting here).
3. When Hgb is not bound to Hp or excreted by the kidneys, it is oxidized to methemoglobin.
   1. The heme dissociates and binds to hemopexin. When hemopexin is depleted, heme will bind to albumin.

Thanks for the help!

#2 on block 1, I'll summarize here:

12-yo girl has a 2-month history of intermittent jaundice. She has both unconjugated and conjugated bilirubinemia. Also - normal haptoglobin, AST, ALT levels. There is no evidence of injury/toxins. Which additional finding is most likely?

So, obviously I ruled out hemolysis immediately (hemolysis would have ↓ haptoglobin)
Then I ruled out "decreased activity of UDP gluronysyltransferase" because of the direct bilirubinemia.
That left me with:
A. Ineffective erythropoiesis → didn't seem to be a likely cause of jaundice
B. Increased alkaline phosphatase → I forget what this even means
C. Gallstones
I chose gallstones because I was thinking ↑ bilirubin would lead to gallstones.
The answer ended up being "decreased activity of UDP gluconysyltransferase" because I guess since the jaundice was intermittent/mostly asymptomatic that automatically points you to Gilbert's syndrome?
Just seems pretty bullshit to me.
Anyway, can someone please explain the right answer and why it's not the 3 answers I was left with? Thanks.

(1) When we appreciate jaundice on a physical exam, are we seeing the deposition of unconjugated or conjugated bilirubin? My guess is unconjugated since it being more lipophilic could deposit into tissues rather than staying intravascularly.

(i.e. does Conjugated, unconjugated, or both, cause jaundice)
(2) Why does jandice start top down? I alway get pimped that the frenulum, then conjuctiva change to yellow first. Also have seen neonatolgist who can guess T-Bili based on how far the jaundice extends (ubilicus is 8 +/- 2). Any reason for this top down predilication? I could just as easily imagine jaundice starting in the feet and working its way up.

When you go to a doctor to check whether you have jaundice or not, he/she will see your medical history and ask you to go for some tests. The results of these tests will help the doctor to diagnose jaundice and know the bilirubin levels. These tests include:

• Liver function test: From the result of this test, the doctor can understand whether or not the liver is functioning properly.
• Bilirubin tests: During these tests, when it is found that the levels of unconjugated bilirubin are higher than the levels of conjugated bilirubin, it suggests hemolytic jaundice.
• Full blood count (FBC) or complete blood count (CBC): The purpose of this test done at a pathology lab in Hooghly is to measure the levels of red blood cells, white blood cells and platelets.
• Hepatitis A, B, and C tests: The doctor suggests these tests for a range of liver infections.

Apart from these tests, there are some other tests that help in the diagnosis of jaundice.

Aims: This study investigated the effect of vitamin E on serum liver enzymes and bilirubin concentrations in male Wistar rats treated with sildenafil citrate (SC) and a combination of SC and tramadol on the background that these drugs cause oxidative damage to the liver.
Methods: Thirty male Wistar rats (180-200 g) were randomly divided into six groups (n=5) thus: control (0.2 ml vehicle – olive oil), SC-treated group (Sil) (10 mg/kg of SC), SC+tramadol-treated group (Sil+Tra) (10 mg/kg of SC and 20 mg/kg of tramadol), vitamin E-treated group (Vit E) (100mg/kg of vitamin E), SC+vitamin E-treated group (Sil+Vit E) (received SC and vitamin E) and SC+tramadol+vitamin E-treated group (Sil+Tra+Vit E) (received SC, tramadol and vitamin E). Drugs were administered orally once daily for four weeks after which blood samples were obtained and used to measure serum concentrations of liver enzymes (AST, ALT and ALP) and bilirubin.
Results: Serum AST, ALT, ALP, total bilirubin (TB) and unconjugated bilirubin (UCB) concentrations were significantly (p<0.001) increased in Sil and Sil+Tra compared with control and Vit E and significantly (p<0.01) decreased in Sil+Vit E and Sil+Tra+Vit E compared with Sil and Sil+Tra. Serum conjugated bilirubin (CB) concentration and percentage conjugation of bilirubin significantly decreased (p<0.001) in Sil and Sil+Tra compared with control and Vit E and increased (p<0.01) in Sil+Vit E and Sil+Tra+Vit E compared with Sil and Sil+Tra.
Conclusion: SC, administered separately and in combination with tramadol altered liver function. However, vitamin E supplementation was able to ameliorate this alteration in liver function.
Biography of author(s)
J. N. Nwangwa
Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, P.M.B. 1115, Calabar, Cross River State, Nigeria.
A. L. Udefa
Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, P.M.B. 1115, Calabar, Cross River State, Nigeria.
P. M. Obi
Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, P.M.B. 1115, Calabar, Cross River State, Nigeria.
C. E. Obeten
Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, P.M.B. 1115, Calabar, Cross River State, Nigeria.
S. Okpa
Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, P.M.B. 1115, Calabar, Cross River State, Nigeria.
Please read full article : - www.journalacri.com

Often in questions, it will say total bilirubin is 5 mg/dl and direct is 2.3 mg/dl is this a conjugated or unconjugated hyperbilirubinemia? This affects the thinking for my differential diagnosis
Before I read it was about 30%+ of the total, and some people have said 50%+, and I looked it up but couldn't find it either. So I was wondering if anyone knows the precise definition?

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.

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

4.0 High 2.1-5.4 Therapeutic

Edited: formatting

• 29
• Male
• 182cm
• 87kg
• Europe
• 1 year
• Gallblader removed

Since last year I had trouble with gallstones (having attacks etc). My gallblader was full of it and was removed 5 months ago.
At that time I did some blood tests and we noticed that my Bilirubin is rising and falling, usually in the range of 2-5.6mg/dl , at one time before the operation, while I was fasting as a preparation for it, my Bilirubin got even to 9mg/dl and I was yellow as Pikachu :) And that's the total bilirubin count, unconjugated is always around 90% of it. For example, I am currently having a cold, and I tested my blood this morning, Unconjugated is around 4.8 mg/dl and conjugated around 0.5 mg/dl.
​
My local docs brushed it of as Gilberts, we didn't do any special tests, just the normal blood work and liver blood tests, and they all came back normal.
​
Can I do some more tests to rule out other possible illnesses because it seems that Gilberts gets diagnosed a lot when there are no other "explanations". The only symptoms I have is that I turn yellow and I feel a bit dizzy the day when I notice that I am having a episode of "Gilberts". I am worried because it seems that the "range" for Gilberts is between 1.2 to 5.3 mg/dl , and that my is slightly above it, and probably never goes down below 2.5.
Would appreciate any advice on what I could do to confirm the diagnosis , lower the bilirubin or talk to my doc and point something out., because it's driving me crazy.
THX! MUCH APPRECIATE!
​
​

Hepatocellular jaundice is basically when the liver is diseased and can no longer conjugate bilirubin, so you have a buildup of unconjugated bilirubin and elevated LFTs.
Obstructive jaundice is when there's something clogging the biliary tree, so you get a buildup of conjugated bilirubin, elevated LFTs, but also elevated alkaline phosphatase. How come alk phos is elevated for the latter but not the former??
Thank you all so much! c:

I was talking about this with a resident today. The direct bilirubin is often raised by a small, clinically insignificant, amount (but enough to exceed the reference range) in hemolysis, jaundice of the newborn etc.
We were discussing the pathofysiological mechanisms behind this phenomenon. At first, I thought it was simple: "More unconjugated bilirubin means the liver has a larger 'pool' of bilirubin it can conjugate, and conjugated bilirubin will rise as a bit as well". But a quick brush-up of bilirubin metabolism reminded me of the fact that conjugated bilirubin immediately gets excreted in the bile, and is not present in the blood in normal circumstances (modern testing has shown that there's virtually no conjugated bilirubin in the blood in normal circumstances. Any direct bilirubin under normal circumstances is actually a false positive for conjugated bilirubin). Does the raised unconjugated bilirubin create a kind of 'overflow' that forces some conjugated bilirubin back into the blood? I couldn't find any documentation on that. Can anyone point me to the correct mechanism?
Or is it a measuring error? I've read that the older staining methods for direct/indirect bilirubin meant that direct bilirubin would get overestimated (because some unconjugated bilirubin will participate in the 'direct' reaction). Is this still a "problem" with more modern tests?