VivaCast 11 – Liver Physiology

FRCA Liver Physiology

Tom and James wade through FRCA Liver Physiology, we debrief afterwards where we try and devise a way to talk about all its functions without listing out something written on our arms!

Checkout Ep 10 – Michaelis Menten – Mass action – Enzyme kinetics for looking at the enzyme kinetic side of the Phase I and Phase II metabolisms.

What are the key functions of the liver relevant to anesthesia?

The liver plays a crucial role in drug metabolism, synthesis of clotting factors, glucose homeostasis, and detoxification. Impaired liver function can affect drug clearance and coagulation during anesthesia.

Intro blurb

The liver is a large, dense glandular organ located in the right upper quadrant of the abdomen, it has wide ranging physiological roles and has significant physiological reserve.

It is divided into four anatomical lobes and 8 physiological segments.

Its 1.5kg in weight, has a dual blood supply and can pool much blood in reserve.

Anatomical particulars

Location

Superiorly you will find the diaphragm, Inferiorly Gall bladder and gi tract, and the pancreas is nearby Posteriorly hepatic vein and IVC, Aorta.

Blood supply

Dual Blood Supply – ie it receives plenty of blood, but some of that blood has tottered past the GI tract first. 75% from Portal Vein 25% from Hepatic Artery Getting 1ml/g/minute of blood – receiving 25% of cardiac output
Both end up delivering 50% of the oxygen requirements for the liver.

Blood transits across the liver

  1. Portal Vein / Hepatic Artery
  2. Portal venules / Right and left hepatic Artery > hepatic arterioles
  3. Hepatic Sinusoids
  4. Hepatic Vein

Autoregulation of flow

Hepatic Buffer arteriole response, when flow via one route into liver drops off, the other vascular supply vasodilates to compensate. It is not reliant on external innervation to achieve this, and is likely achieved by adenosine at vascular smooth muscle level.

Capacitance role

The liver can constrict, alongside the splanchnic, pulmonary bed and spleen to add extra blood to the circulation in times of claret poverty

Bilious drainage

From an acinus the bile canaliculi drain via > Peri-portal cholangioles> Intra-lobular bile ductules> Intra-hepatic bile ducts > Right and left bile ducts > Common Bile Ducts > Cystic duct +pancreatic Duct > Ampulla Vater > Duodenum

Physiological roles

There is a liver Lobule – that carries no defined role

There is a Liver Acinus – which is the functional element.

Blood flow across this functional unit

Portal tract out to central veins Counter flow of Bile drainage along bile canaliculi adjacent to the portal tract The hepatic artery tracks up alongside the portal tract

This cluster of tracts into the system cross a network of hepatic sinusoids lined with hepatocytes and other cells. before draining into bilious and central venules.

The capillary structures here are sinusoidal and therefore exceedingly porous to most molecules found in the blood supply.

These sinusoids are broken down into Zones!

Hepatocyte Zones

Nearest the portal / arterial tract (most oxygen)

  • Zone 1 – Busy, dense with mitochondria – involved in glycogen synthesis and oxidative metabolism
  • Zone 2/3 – Biotransformation of drugs / CYP 450 / Favours anaerobic process
  • Zone 3 – Highest risk of ischaemic injury in hypo-perfused states.
    Furthest the portal / arterial tract (least oxygen)

Specialist Cells found in the Liver

Stellate Cells – Vitamin A Storage – contractile when exposed to vasoactive substances

Kuppfer Cells – Specialist hepatic macrophages

Liver Roles

BioTransformation

Aims to make molecules either more water soluble or lipid soluble for bilious clearance

Phase I

Reduction / Oxidation / Hydrolysis P450 Cytochrome System If a polar, water soluble metabolite is achieved it is cleared renally

Phase II

Conjugation / Glucoronidation / De-Methylation / Sulphation / Acetylation If rendered water soluble, then renal elimination If rendered less soluble ‘non-polar’ then cleared via Bile

Cytochrome p450

A Gene Superfamily of Haem containing molecules, with the iron moiety being the active bit. Found in the hepatocytes endoplasmic reticulum.

Bile Formation & Secretion

500-1200ml/day of Bile is produced , it is made of inorganic electrolytes, bile acids, phospholipids, bilirubin, cholesterol, it is alkaline, and aids in absorption of vitamins ADEK.

Knackered RBCs can’t transit the reticuloendothelial system of the spleen get broken up freeing haemoglobin – haem / globin are split and the globin reutilised.

Hame is oxidised by free oxygen molecules, the iron molecule is liberated by enzymes becoming biliverdin (Green) Biliverdin >> subsequently converted to bilirubin by biliverdin reductase >> Subsequently taken up by hepatocytes, conjugated and excreted into GI tract, some is reabsorbed having been deconjugated by GI tract microbes and cleared renally, the rest is converted to stercobilinogen (brown poo colour!)

Immune function

Gi Tract Antigens – that cross into the portal circulation end up having to transit the liver which acts as a filter.

These antigens must elude the Kuppfer cells, as well as Natural killer and Natural killer T Cells Plus well as the complement system and its forever hunt for pathogen associated molecular patterns (PAMPS)

Lactate Management

Cori Cycle mops up lactate, which is a by product of oxygen scant ATP production . Glucose > Glycolysis > Pyruvates

Pyruvate converted to lactate by lactate dehydrogenase,

Lactate is shifted back to pyruvate by lactate dehydrogenase but requires NADH > NAD in process, chiefly taking place in liver, but also somewhat in muscle and also kidneys.

Pyruvate fed back into TCA cycle.

Carbohydrate management

  • Glycogen storage
  • Conversion galactose and Fructose to glucose
  • Gluconeogenesis

Lipid Management

  • Oxidation of fatty acids, synthesis of cholesterol, phospholipids and lipoproteins
  • Fat broken down into its fatty chains and its glycerol element. Fatty acids undergo beta oxidation > acetyle coA

Urea (protein)

The liver is exceedingly busy with proteins, and a byproduct of this is ammonia

Ammonia is quite bothersome and toxic, and this is another of the livers many jobs, tidies it up.

Ammonia = NH3, at ph7.4 NH3 ionises to NH4+ (Ammonium – rocks about causing havoc if left unchecked)

Converting this into urea is done so in the mitochondria of hepatocytes, many steps we ain’t biochemists.

Ammonia (and other byproduct) accumulation in liver failure causes hepatic encephalopathy.

Synthetic Liver Function

  • Haptoglobin – Mops up free Hb
  • Haemopexin – Mops up Haem
  • Transcobalamins – for b12 management
  • Caeruloplasmin – mops up free copper
  • Transferrin / Ferritin for Iron transport
  • CRP – complement friend
  • Complement synthesis
  • Alpha1 anti-trypsin
  • Albumin
  • Clotting Factors

No liver section is complete without paracetamol

Paracetamol normally tidied up by being 95% glucoronidated to paracetamol conjugates 5% of it goes through CYP450 route becoming a toxic intermediary –  N-acetyl-p-benzoquinone imine (NAPQI!)

Normally glutathione mops up NAPQI

But if there is far too much paracetamol about the place, the glucoronidation system becomes overwhelmed and more and more NAPQI accrues.

NAPQI goes on a hepatotoxic rampage

Glutathione is a thiol – it has a proclivity for binding metabolic intermediaries that would otherwise get up to no good.

Glutathione S-Transferase catalyses the reaction.

N-AcetylCystiene (NAC) is the treatment here,

NAC offers up cysteine, which when metabolized with glutamate, forms an intermediary (gamma-glutaylcystiene) this is subsequently metabolized with glycine to glutathione, which mops up the NAPQI

In an easier to read form

NAC offers up Ccysteine + Glutamate >>glutamate-cysteine ligase (GCL)>> γ-glutamylcysteine+ Glycine>> glutathione synthetase (GS) >> Glutathione


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Transcript

Gas, Gas, Gas Episode 92: Liver Functions and Physiology

Introduction and Episode Overview

00:00-01:40

Please listen carefully. Hello and welcome to Gas, Gas, Gas, the podcast that covers the FRCA primary exam. We’re going to fit into your day and give you as much of your life back as you could possibly imagine. I’m here to make your studying easier. Listen to us on your commute, in the gym, in the shower, or when you’re ironing your scrubs. Expect facts, concepts, model answers and the odd tangent. Check out the show notes for all the detail, and remember to follow the show so that you never miss an episode. Let’s get on with it.

So, naturally, after quizzing Tom mercilessly for the last two hours, I thought the best final closing question would be to ask him about the nebulous, expansive and delightfully mysterious roles of the liver. Because it’s a challenging one to talk about, because it’s so deeply embedded across so many different pathways in your body in terms of maintaining homeostasis – well in excess of what the kidneys really do – that it’s absolutely fair game to bring up in an exam, because it’s an exceptional challenge to convey in an ordered manner.

Tom has a good crack at this, and at the end I’m going to talk a little bit about its roles. Have a look at the show notes, read the chapter on livers in any textbook you may choose, so that you have half a chance of in a concise and ordered manner delivering on this question well. If you have the misfortune to get it, if you are prepared and you get it, you’re going to shine.

Basic Liver Anatomy and Function Overview

01:41-02:49

Summary: Tom provides an initial overview of the liver’s location and broad functions.

So moving on to the final section of your physiology viva here, Tom. I hope you’re ready for it, because I certainly am. What on earth is the liver?

The liver is a large glandular organ sitting beneath the right hemidiaphragm that’s involved in multiple metabolic and physiological processes. So it has functions as a capacitant. It has a detoxifying role in terms of metabolism. It’s an important part of glucose homeostasis. It has synthetic functions, which include lots of protein production – importantly albumin, but also clotting factors – and has haematologically important function on that basis. And it also produces bile and aids, therefore, in the metabolism and absorption of fat-soluble vitamins from the GI tract. It’s also immunologically important for its synthetic function and production of immune proteins as well.

Liver Blood Supply and Drainage

02:49-03:25

What’s its blood supply?

The liver receives its blood supply through the portal vein and the hepatic artery. It’s unusual in that it receives around 60% of its oxygen supply via its venous supply through the portal system under normal circumstances, and the remainder via the hepatic arterial system. This is due to its specific function of detoxifying things absorbed through the GI tract via the portal venous system.

Okay, and its venous drainage?

And its venous drainage is via the hepatic vein into the IVC.

Bile Production and Bilirubin Metabolism

03:25-04:39

Summary: Discussion of bile production, storage, and the breakdown of haemoglobin to bilirubin.

So you mentioned it processes bile. Where does bile come from?

So bile is produced by hepatocytes and is then transferred and stored via the biliary system in the gallbladder. The liver itself is made up of functional units consisting of… Sorry, what metabolic by-product ends up being converted into bile?

So cholesterol is important in the production of bile, but bile salts and bile – importantly metabolising the breakdown of haemoglobin.

Can you talk me through that?

As red blood cells are broken down, they produce bilirubin, which itself is unconjugated. When it reaches the liver, it is conjugated. This bilirubin is then used in bile production and transferred to the GI tract, where it undergoes further changes into products such as stercobilin under the influence of bacteria within the GI tract, expelled in the faeces. Some is also reabsorbed as well.

Biotransformation and Detoxification

04:42-06:43

Summary: Tom explains Phase I and Phase II metabolism, using paracetamol as a key example.

And then you mentioned biotransformation and detoxification there, Tom. Could you just talk me through the different systems involved?

So detoxification primarily can be thought of as Phase I reactions, importantly mediated by the CYP 450 superfamily of proteins produced in the liver. This includes reactions such as oxidation, chemically changing things absorbed from the GI tract, or drugs sometimes administered to us in order to make them metabolically inactive. Although in some special situations those reactions can make things pro-active, such as prodrugs like codeine.

Then to remove these products, we have Phase II reactions which aid in the body’s ability to remove and expel products of those substances, so making them water soluble in order that they can be removed by the renal system, or some fat soluble things can be removed in the bile and expelled in the faeces via the GI tract.

So you mentioned Phase II reactions and conjugation. Talk me through how paracetamol is metabolised.

Paracetamol is primarily metabolised via initial transformation into a toxic metabolite, which is then further detoxified by the presence of glutathione, which glucuronidates the paracetamol in the liver, and then allowing for its removal. This system can be saturated, so if your glutathione stores are completely used up, then you get accumulation of the toxic metabolite of paracetamol, and this can lead to direct hepatotoxicity and damage of hepatocytes, which is suboptimal.

Glucose Metabolism and Hormonal Control

06:45-09:00

Summary: Tom discusses the liver’s role in glucose homeostasis, insulin and glucagon mechanisms.

And going further about these synthetic and metabolic functions of the liver. You mentioned its role in glucose metabolism. How is that controlled?

So, glucose homeostasis is maintained by the interaction of hormones such as insulin and glucagon on sensitive peripheral cells. Musculoskeletal cells – I beg your pardon, skeletal muscle cells – originally thought of as being important in this, but actually the liver is probably the most important sensitive tissue to the influence of insulin.

So glycogen stores within the liver can be used to produce glucose in the blood under the influence of glucagon or in the absence of insulin, and at higher levels of insulin in the blood this process can be reversed and glycogen can be stored within the liver for use at a later time.

Sorry, just to clarify for me. What is the source of glucagon and insulin?

So insulin is produced in the islets of Langerhans within the pancreas by pancreatic beta cells, and glucagon is also produced in the pancreas by the alpha cells.

And how does insulin exert its effect?

So insulin exerts its effect via tyrosine kinase receptors on the surface of sensitive cells. When it binds to two receptor sites linked to the same transmembrane protein, this causes activation of downstream cytoplasmic reactions that lead to the cellular intracellular effects of insulin.

So, within the liver, this can cause production of glycogen from glucose stores within the cells, but also within skeletal muscle they result in the uptake of glucose within those cells in order to produce energy.

And that is your time up.

Post-Viva Discussion and Feedback

09:00-15:54

Summary: Tom and James discuss the challenges of structuring liver physiology answers and strategies for improvement.

Could have gone a bit worse. I always feel like it’s a terribly long list of things that the liver does, which is why I deliberately, when you mentioned we were going to do something on the liver, I had a piece of paper ready so that I could not repeat myself and try and remember all the things, but I didn’t use it. But I mean, I don’t think I missed anything major.

I think you covered them all, but it was still a bit lacking in structure, and it’s probably worth having a structure because, like, for me, for the kidney, I think about it as like its waste effects, its metabolic effects, its hormonal effects. So, maybe break the liver down into that as well. Yeah, what do you think you might do?

I think it’s one that’s probably worth practising out loud some more. ‘Cause I think the main ones I talked about – the thing that makes me a bit unstructured, I think, is because I haven’t practised and because there is some overlap. So people obviously sometimes will talk about haematological or clotting function, and then talk about synthetic function separately and immunological function separately. But in a way, they’re all just synthetic function, they’re just production of proteins with different functions.

But it doesn’t really matter so long as you’ve practised and you know what you’re going to say. Whereas if you’re sitting there going, “oh, shall I stick that in this category or that category?” It makes it slower, and you can miss marks if you’re slow, and it just is like you say, just feels less structured.

Because, yeah, I agree with the feedback, it felt a bit – a little bit here, a little bit there, and a bit slow in places.

Could you go with like dietary function, homeostatic function, immunological function? Because homeostatic then really is an umbrella term for the albumin synthesis, the clotting factor synthesis, the acute phase reactant synthesis, the gluconeogenesis and glycogenolysis, and all that sort of stuff. And then I suppose your third or your fourth one would be its biotransformative function or metabolic function. What do you think?

I’ll have a think about it. I think there’s no escaping that it’s quite a long list, is the problem. Yeah. That’s the thing.

One way of doing it would be not to mention all the synthetic functions at the beginning, just to say – I could say something along the lines of – I’m sorry, I’m practising out loud on the podcast now, but that’s fine, people are listening. Something along the lines of: “the liver has functions in the biotransformation of chemicals in the body, has multiple synthetic functions, it has capacitance function within the cardiovascular system, and it has an important role in the metabolism of glucose and its products.” Is that enough?

It’s hard, isn’t it? I’ve just thought of it. Yeah, and then you could say, and then you can go back and break down “the synthetic functions are multiple and they include production of clotting factors, immune proteins.” Or you could frame it as clearance of waste and biotransformation because then you won’t forget bile and bilirubin and all that jazz.

I might – you might even open the door and say “the functions of the liver are extensive” because then that’s like a slick way of saying “buckle up, here’s a list coming.” Yeah, I mean, I don’t know how much that helps, but yeah, it gives you a moment to think. I think it does, and then it kind of like frees you up to be like, well, there are lots of things to say, so I’m not going to get stressed if I’m still talking in 30 seconds’ time because it’s like managing yourself as well as all the other things, isn’t it?

But I do think what I had planned to do in my head was write the list down. So then you can not forget what you’ve already said and go through systematically for the examiner. So if I put numbers and the names of those categories, I think it automatically is a bit more structured, and you can’t waste loads of time doing it.

But I think it is a big enough one that it’s a bit tricky to keep track sometimes while you’re trying to think of the next bit of what you’ve already said. And if you say your things, write them down, and then go back and do them in the same order, it’s automatically more structured than me reeling off a list, which is what I think I did, and then going back to the different parts of it in a different order.

I think if you can draw a schematic incredibly quickly of, like, a liver, a pancreas, a spleen, and a GI tract, then you could probably just put some arrows for like drugs and immune system stuff. And like, as long as you can draw it really quickly, it’ll probably help everything hang off, I suppose. But you don’t want to get bogged down drawing a liver – “that doesn’t look like a liver, I best write liver” – you’re getting stuck.

It’s always worth when there’s an organ question, you did most of it, is just say where it is, what it is, what the blood supply in and out is as like your little opener, so that they just move you on. I mean, you could like sometimes they quote like the amount of cardiac output it receives and all that sort of jazz, but all those things don’t add up to 100%, it seems. Like, if you add up 25% for liver and this much for the brain, and that much for the kidney and such, I’m sure it adds up to more than one hundred percent.

Yeah, I’ve wondered that before. But yeah, where it is, what plumbs it in, important other structures nearby. So like there’s a gallbladder, there’s a diaphragm like you mentioned.

What is the percentage of cardiac output to the liver of interest? Have you got a number?

Apparently twenty-five percent.

Right, well Tom. Well done. That was your physiology viva. You survived. Yeah. That grin is just about still there, is it? Just, just.

But the liver is so extensive that if you get a question on it, they’re probably not going to drill down into one particular thing really deep, they’re probably going to try and keep it broad and somewhat relevant to anaesthesia and the practice of critical care perioperative medicine. Yeah, okay.

I’m gonna look at it, I’m gonna practise that one, structure it. And I’m going to look again at gluconeogenesis and glycogenolysis and all that, because I probably could have given a quicker, slicker answer to that, yeah, definitely. Because if you’re saying a hormone, like say where it comes from, because otherwise, they have to ask, and then so just like “glucagon alpha cells of the pancreas,” bang, yeah, just let it come out right at the beginning, then you don’t have to go back.

All right, good stuff. All right, nice one, James. Thank you very much, and I hope you’re gonna come back for more. Yeah, see you again for the next one. Yeah.

Host’s Comprehensive Liver Review

15:55-25:59

Summary: James provides a detailed, structured approach to answering liver physiology questions.

Your opening gambit, everyone, on a question about “tell me about so-and-so organ” should probably break down into its blood supply, its anatomical location, its broad roles before then dipping down into some nitty-gritties. You might choose to describe a functional unit – for example myocardium, you might talk about the excitation-contraction coupling. But you really need to be guided by what the examiner wants. Otherwise, you might go down a squirrelling rabbit hole where they can’t really get a word in edgeways. You’ve prepared too much, and then you run out of time.

So, have an opening gambit where you reel off a few things that just get the conversation rolling.

Anatomical Overview

So for the liver, I describe it as a large, dense, glandular organ. It’s located in the right upper quadrant of the abdomen. It has wide ranging physiological roles, and it has significant physiological reserve in itself if damaged. It is divided into four anatomical lobes and eight physiological segments. It is about one and a half kilos in weight.

Superiorly to the liver you will find the diaphragm, or the right hemidiaphragm. Inferiorly the gallbladder is associated with it, and you will find some GI tract including the right hepatic flexure of the large bowel. Posteriorly you will locate the hepatic vein, inferior vena cava, and the aorta.

Blood Supply Details

It has a dual blood supply, and this is very particular to the liver. It receives blood flow from the portal vein as well as the hepatic artery. Seventy-five percent of its blood flow is portal vein, twenty-five percent of its blood flow is hepatic artery. Overall, it receives 1ml per gram per minute of blood, and is approximately twenty-five percent of the cardiac output.

Each element of this blood supply, portal and hepatic, offer up fifty percent of the oxygen requirement of the liver. An interesting side note here, guys, is there’s an interesting auto-regulatory flow system called the hepatic arterial buffer response, whereby, if the liver notices that the hepatic artery blood flow or the portal vein blood flow tapers off, it triggers vascular smooth muscle relaxation in the other supply in an effort to maintain blood flow to the liver. Clever.

Hepatic Blood Flow and Functional Units

So the liver has a multitude of roles, which I’m going to get into, but I first want to describe flow of blood across the liver. So blood flow enters the liver via a portal vein or hepatic artery, as we’ve just discussed. You will then find that portal vein breaks down ultimately into portal venules, and the right and left hepatic arteries then split further again into hepatic arterioles.

Blood then ultimately flows through hepatic sinusoids – heavily fenestrated leaky capillary beds lined with hepatocytes – before then being reaccumulated in hepatic veins draining off into the IVC and back off to the right side of the heart.

You can imagine then there’s quite a lot of blood in the liver, and the liver does play a capacitance role in delivering an extra bolus of blood to a system undergoing haemorrhage with sympathetic mediated vasoconstriction of the liver and the splanchnic bed. Other bits of the body that do this are your spleen and your pulmonary vascular bed as well.

We don’t want to miss out on another route of drainage out of the liver, which is the biliary system. There are canaliculi – i.e., very, very fine ducts – that gather up debris from these hepatocytes in a functional unit of the liver, which I’m about to go into.

Liver Acinus Structure

So the functional element of a liver is called a liver acinus (A-C-I-N-U-S). There is blood flow across this unit, and this blood flow goes from central to outward. It’s shaped a little bit like a hexagon maybe. The bile is collected in a countercurrent manner and as you can imagine, all the cells that are very central to this portal and arterial blood flow get plenty of oxygen, whereas the cells creeping to the outside on the more venous end of this functional unit get less oxygen. You can subsequently imagine that those little fellows are more susceptible to hypoxia.

Some clever person has broken these groups of cells down into zones and classified their roles in a little bit more detail. As you can imagine, the ones that have a better oxygen supply are probably a bit more metabolically busy doing things that require more oxygen.

So Zone I, nearest this good blood supply end, very dense with mitochondria, quite busy, involved in glycogen synthesis and oxidative metabolism of things. Remember you’ve got your Phase I, your Phase II metabolisms. The middling zone and the outer zone are a bit more involved in biotransformation of drugs, more cytochrome activity, and tipping towards more of the anaerobic stuff. As you would imagine, Zone III, the most outer element of this area, is the highest risk of ischaemic injury.

Phase I and Phase II Metabolism

Remember that Phase I is reduction, oxidation, and hydrolysis of bits and pieces. If Phase I successfully manages to convert something into a polar and water-soluble metabolite, then typically these are cleared renally. If, however, it doesn’t really make it far enough to this, then things kicked out of Phase I may undergo Phase II metabolism too, where they might get conjugated, glucuronidated, demethylated, or sulphated, acetylated, with the goal of trying to render these things water soluble so they can be cleared by the kidneys.

If they don’t, they end up considered a non-polar molecule – i.e. one that’s a bit better at dissolving into fats – and these are cleared via the biliary system into the GI tract.

Structured Approach to Liver Functions

As we said with Tom, how on earth are you going to go through the plethora of roles the liver finds itself doing in the body without waffling on for hours? You probably need to sit down and write this all down on yourself to figure out exactly, but I’m feeling that I’d be tempted to say that you could go through:

  1. The nutrient management roles of the liver
  2. The synthetic productive roles of the liver
  3. The metabolic drug clearance and waste product roles of the liver

You could then discuss how the liver manages carbohydrates – gluconeogenesis, glycogenolysis, glycogen storage – its lipid metabolism, including cholesterol synthesis, etc., its protein management, which would then let you segue on into the waste products of protein management, including production of ammonia, which is managed into urea by the liver to make it less toxic and more readily clearable.

This would let you step into the lactate side of things and the Cori cycle, before then moving into metabolism of other agents, drugs, etc., and closing out with the synthetic functions of the liver.

Synthetic Functions

Those being albumin production, clotting factor production, producing the proteins to store and utilise iron – transferrin, ferritin, haptoglobin for mopping up haemoglobin – and its CRP producing role.

You could then from here discuss quickly its immune surveillance function of materials coming via the GI tract to the central circulation with the Kupffer cells and other specialist immune cells that ensure a reduction in the odds of bacterial contamination from your GI tract to your circulating blood.

And then you mentioned haptoglobin there, and then you could talk about haem management, bilirubin production and how that is eradicated from the blood.

And if you can reel all that off, you’re probably most of the way there. They might then ask you about paracetamol, which is a lovely one to talk about, isn’t it? If they’re being real pests, maybe, I don’t know, Wilson’s disease. It’s worth having a think about this yourself, though.

Anyway, thank you for listening. I hope this was useful. See you next time.

Closing

26:00-26:17

Thanks for listening to the episode, guys. If you found it useful or awful, please like and subscribe and rate the show. Definitely, go check out the show notes on gasgasgas.uk. We all know that this is a bucket of content. I want you to take some time for yourself and don’t overcook it. Don’t freak out, keep studying.



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