Block 4 week 10

how many functional segments of the liver are there?

9

why is it said that the liver has dual blood supply

receives:

• oxygenated blood from heart via hepatic artery

• nutrient rich slightly deoxygenated blood from from gut via hepatic portal vein

liver is composed of smaller structures called lobules. what are lobules surrounded by?

branches of hepatic artery and portal vein

what are sinusoids?

specialized capillaries with large pores

sinusoids have increased permeability compared to capillaries what does this mean about the type of molecules which can cross

it allows larger molecules such as proteins to cross

how is increased permeability of sinusoids achieved

• incomplete surrounding basement membrane.

• endothelial layer contains large intercellular gaps

What are kuffer cells?

macrophages in the liver

what are sinusoidal endothelial cells?

line the sinusoidal blood vessels

what are stellate cells?

found in peri-sinusoidal space, activated in response to damage

What are hepatocytes?

liver cells - which are extremely metabolically active

What are cholangiocytes?

epithelial cells lining the bile ducts

what is released in amino acid break down which is potentially toxic

amine group

how does the liver remove the amine group from amino acids which is potentially toxic?

deamination
converts it to urea which is a harmless product which can then be excreted by kidneys

what if excess glucose stored as

glycogen

what does the liver convert excess carbohydrates and proteins to?

fats

what are the different type of lipoproteins export cholesterol to cells

HDL and LDL

what is a surplus of cholesterol converted to?

bile salts by the liver

Retinol is carried in the bloodstream bound in a complex with TTR.
what is TTR?

a protein made in the liver

what is vitamin a important for?

eye health

in some immune cells retinol is converted to retinoic acid why?

retinoic acid is very metabolically active and can be delivered to cell which need it

how are toxic compounds made easier to excrete

often toxic compounds are fat soluble so by converting them into water soluble compounds they are easier to excrete

what are the two steps of detoxification?

phase 1: fat soluble toxins are processed by oxidation, reduction and hydrolysis reactions
phase 2: toxin or metabolites from phase 1 is conjugated to another compound which is less harmful and makes it more water soluble so can be excreted easily

phase 1 detoxification produces free radicals. what neutralises them?

antioxidants

which plasma proteins are produced in the liver

albumins
globulins
fibrinogens

What is the role of albumin?

regulates osmotic pressure

what is the role of globulins?

transport and antibodies

What is the role of fibrinogen?

part of the clotting cascade, forms a fibrin clot

where is bile produced?

liver

bile is secreted into the small intestine by \----------

hepatocytes

cholangiocytes modify bile \______________ and composition

volume

what is the purpose of bile

To emulsify lipids increasing the surface area for lipases to act

how is bile recycled?

bile salts which enter the small intestine can be reabsorbed into the hepatic portal vein

what is a colloid?

a homogenous non-crystalline substance consisting of large molecules of one substance dispersed in another

what are the two categories of colloids?

lyophilic and lyophobic

what are the characteristics of lyophilic colloids?

• affinity for medium is high (like solvent dispersed into)

• spontaneous formation of colloidal dispersion

what are the characteristics of lyophobic colloids?

• do not like solvent dissolved in

• needs energy to be provided

• preparation requires breaking large particles into particles of colloidal dimensions

what are the different preparation methods for colloidal dispersions?

dispersion method:

• colloidal mill

• ultrasonic treatment condensation methods:

• supersaturated solutions

colloids are polydisperse. what does this mean?

multiple different size and shape particles

colloids can form many shapes. give some examples of the different polymers which could form these shapes

• Lipophilic polymers when in water tend to form long chains which are coils

• Proteins such as albumin are spherical

• Peptides and short fragments of DNA can be seen as rods

what is viscosity

the resistance to flow

what can light diffraction be used to determine?

size and molecular weight

ionic substances will be charged by an (equal/unequal) dissolution of the opposite charged ions? is the correct word for this sentence equal or unequal

unequal

what is the charge of the colloid controlled by?

the ionisable surface grouping

what is ion adsorption in relation to colloids?

the net surface charge acquired by unequal adsorption of the oppositely charged ions

what do frequent encounters between colloids lead to?

coagulation
aggregation
flocculated particles
dispersed particles

what factors effect the stability of lyophobic colloidal systems

electrical forces of repulsion
forces of attraction

what factors effect the stability of lyophilic systems

solvation

in a lyophilic colloid:
if the primary maximum is greater than the thermal energy then the system is stable and if the primary maximum is less than the thermal energy then the system is unstable. what does an unstable system lead to?

formation of aggregates

what happens to lyophobic colloidal systems when electrolytes are added

No electrolytes there is maximum repulsion
Adding electrolytes will lead to weakening of repulsive forces and a generation of primary maximum and a secondary minimum
Adding too many electrolytes will lead to system being destabilised as collides are able to get into contact

lyophilic colloid systems use a combination of electric double layer interactions and solvation, how is this destabilised

adding high amount of electrolytes, water of solvation is lost leading to salting out effects

polymer materials can adsorb on surface and stabilise lyophobic colloidal systems how?

by steric interaction between particles leading to repulsion - entropic stabilisation

what are dispered systems

a dispersed system consists of particles in one phase dispersed in another

why is a large surface area to volume ratio needed in a dispersed system

as the dispersed phase is never solubilised on the continuous phase leading to surface tension which needs to be reduced

how can surface tension of dispersed phase be reduced?

particles associating and aggregating

what are polymers?

macromolecules made of monomers

what is a monomer which carries a charge called?

an electrolyte

what does mean when it says polymers are poly dispersed?

some chains will be longer than others

what is a homopolymer?

a polymer made of a single monomer

What is a copolymer?

a polymer made up of different monomers

what happens to the viscosity of the solution if a hydrophilic polymer was placed in water?

the viscosity will increase as the polymer will attract water molecules

what happens if a hydrophilic polymer was placed in an organic substance?

will minimise the surface area to reduced the surface tension

why can very large polymers show crystalline region at high concentrations?

as the order between monomers can mimic the organisation of crystals

give some examples of the uses of polymers

• excipients in tablets

• coating

• controlled drug release

• excipients in semi- solid preparations

• adhesive polymers for skin delivery

how are gels formed?

aggregation of colloid solid particles.
- particles are often polymers which form an interface network

how is gelation obtained

having a continuous floccule. Floccules are loose aggregates of sols obtained at specific experimental conditions in which attractive and repulsive forces allows for solids to come in close contact, move together but then dissociate after a while

what are the two types of lyophilic gels

type 1 ( chemical)
type 2 (physical)

how do surfactants work?

Reduce the surface tension by placing themselves at the interface of interest as surfaces have two distinct regions: hydrophobic and hydrophilic (said to be amphipathic)

what are the different types of pharmaceutical uses of surfactant

stabilise emulsions, formation of suspensions, improve wetting of solids, used in drug delivery systems, stabilise monoclonal therapeutic antibodies

name the 4 types of surfactant

anionic
non-ionic
cationic
zwitterionic

what is the difference between a regular micelle and an inverted micelles

with a regular micelle the hydrophobic tail is on the inside and the hydrophilic head is on the outside whereas with inverted micelles the hydrophobic tails is on the outside and the hydrophilic head is on the inside

explain how micelles form

• Adding surfactant in aqueous solution move to the interface and start to decrease the surface tension

• The more surfactant added the more the surface tension is decreased. This is true until interface is covered.

• When interface is covered additional surfactant added cannot move to the interface so start to form micelles

what are the three main course of liver disease?

alcohol
non-alcoholic fatty liver disease
viral hepatitis

what is the advice for drinking alcohol

it is recommended to not drink more than 14 units of alcohol a week and it should be spread across three or more days

fats are metabolised in the liver to form \_____________ which are released into the circulation

lipoproteins

what happens when there is an excess of triglycerides or blockage of the release of lipoproteins?

there is a build up of fat in liver cells

what are some risk factors of non-alcoholic fatty liver disease (NAFLD)

• obesity

• increased visceral fat

• insulin resistance

• lack of exercise

what are the four stages of NAFLD?

1.accumualtion of fat in cells 2. inflammation due to accumulation of fats 3. inflammation has led to scarring in the liver 4. irreversible liver damage

can hepatitis A progress to chronic liver disease

No

hepatitis D can only replicate in presence of hepatitis B what does this combination lead to?

increased risk of progression of liver disease

why is hepatitis C known as the silent killer

the majority of those who are diagnosed are asymptomatic, and it leads to slow progressive liver disease

do patients with pre-existing liver disease have increased susceptibility to develop hepatotoxicity

no they do not have increased susceptibility they may be more severe due to reduced hepatic reserve

what is a intrinsic reaction (drug induced liver disease)

• predictable

• dose dependent

• occur very rapidly

• tend to cause acute liver failure

What is an idiosyncratic reaction? (drug induced liver disease)

• unpredictable

• not dose dependent

• take longer to occur

• results from an metabolic idiosyncrasy or immunological reaction

• can cause any type of liver injury

what is acute liver disease

symptoms do not exceed 6 months

what is chronic liver disease

symptoms persists more than 6 months

What is cholestasis?

disruption of bile flow

what is hepatocellular damage

injury to hepatocytes

• fatty infiltration

• inflammation

can a patient have both cholestasis and hepatocellular damage?

Yes a patient may have a combination of both. Understanding damage is from cell or bile duct is important to see how sever liver disease is

both cholestasis and hepatocellular damage can lead to fibrosis and cirrhosis. what are these?

fibrosis is the persistent, extensive hepatocyte damage which leads to the formation of scar tissue.
cirrhosis is the most severe form of liver damage. it is scarring of the tissue which prevents liver from carrying out normal functions

what is compensated cirrhosis?

there is enough capacity to perform functions

what is decompensated cirrhosis?

does not have enough capacity to perform required liver functions

what are some signs and symptoms of liver disease?

jaundice
pruritus
pale stools and dark urine
spider naevi
bruising and bleeding
liver palms
finger clubbing
ascites
encephalopathy
portal hypertension

what are the core liver blood tests?

bilirubin
alubumin
alanine aminotransferase/aspartate transferase
alkaline phosphatase
gamma-glutamyltransferase

what is ascites

accumulation of fluid in the peritoneal cavity leading to swollen abdomen

• A role of albumin is keeping fluid in blood vessels

• When not enough albumin is present in blood vessels Fluid is more likely to leak out into the tissues, particularly around the abdomen

what is the treatment for ascites

Spironolactone (aldosterone antagonist) + furosemide (loop diuretic) and NaCl secretion.

what is spontaneous bacterial peritonitis?

infection of ascitic fluid without intra- abdominal source of sepsis

What is hepatic encephalopathy?

Neuropsychiatric changes including changes in mood and behaviour, confusion, delirium and coma that occurs as a result of liver failure

what is the rational behind using laxative as treatment fro hepatic encephalopathy

inhibits intestinal ammonia production reducing the colonic bacterial load

what is the cause of portal hypertension

there is increased resistance to flow due to:

• disruption of hepatic architecture

• compression of hepatic venules by regenerating nodules

what is varices

Body forms new weak blood vessels forming of current blood vessels in aim to relive pressure. Eventually blood vessels will burst because they are very weak resulting in GI bleeding which can be vert severe due to large amount of blood