Studied by 0 peoplefunctions of the liver
bile production, metabolism, detoxification of blood
where does the coeliac artery lead to
stomach, spleen and hepatic artery
where does the superior mesenteric artery lead to
intestine and pancreas
where does the inferior mesenteric artery lead to
(lower) intestine
where does the liver receive blood from
hepatic artery and portal vein
how much bile does the liver produce daily
250-1500ml
what are the major secretions of hepatocytes
bile salts, phospholipids (lecithin), bile pigment (bilirubin), cholesterol, inorganic ions
why are hepatic sinusoids leaky
allow more contact between blood and hepatocytes
what is the role of bile salts from hepatocytes
used in lipid digestion and absorption
where do bile salts derive from
cholesterol
circulation of bile salts
liver synthesises
bile salts to gall bladder and duodenum
moves through duodenum to ileum
bile salt removed from ileum by entering hepatic portal vein or removal in faeces
bile salts in hepatic portal vein recycled to liver (where some synthesis occurs again)
where do bile pigments come from
breakdown of haemoglobin conjugates with glucuronic acid
use of glucuronic acid in bile pigment formation
increases polarity and solubility in water
how does bile enter the gall bladder
bile flow to duodenum is prevented by closures of sphincter of oddi so will instead enter gall bladder
why do bile salts and pigments become concentrated in the gall bladder
reabsorption of water and salt in gall bladder
what causes sphincter of oddi relaxation
CCK and neural influences (CCK causes sphincter to relax allowing bile into duodenum as well and pushing some bile out of the gallbladder)
when will bile pass to the duodenum instead of the gall bladder
after a meal
when will bile pass to the gall bladder instead of the duodenum
during relaxation
where are lipoproteins formed
liver
where are plasma proteins and clotting factors synthesised
liver
effect of less albumin in blood
more leakage of water to outside of cells (ascites)
liver endogenous molecules that are controlled
insulin, glucagon, aldosterone, female sex hormones
liver exogenous molecules that are controlled
drugs (some converted to active compound)
mechanisms involved in liver metabolism
oxidation, reduction, methylation, conjugation
describe jaundice
bilirubin accumulation in plasma producing yellowing of skin, sclera and mucous membranes. may produce kernicterus which can lead to nerve degeneration in brain
treatment of jaundice
light (breaks down pigment)
describe haemolytic jaundice
excessive haemolysis of RBC (reaches capacity for excretion of RBC)
describe intrahepatic jaundice
defects in conjugation or secretion of bilirubin by hepatic cells (common in acute)
describe obstructive jaundice
blockage of bile ducts
describe physiological jaundice of newborns
babies have poor capacity for conjugating biluribin
what causes acute hepatitis
hepatitis A, B, C (viral) and drugs (eg paracetamol)
what causes chronic hepatitis
hepatitis B, C (viral)
define cirrhosis
necrosis of liver cells replaced by fibroblasts
causes of cirrhosis
alcohol, hepatitis B and C
treatment for cirrhosis
no treatment, just stop causative effect (or organ transplant)
describe layers of GI tract from lumen to outside
mucosa, submucosa, submucosal plexus, inner circular muscle, myenteric plexus, outer longitudinal muscle
name of GI pacemaker cells
interstitial cells of cajal (ICCs)
what rhythm do ICCs pacemaker cells form
basal electrical rhythm (BER)
what does VIP do to smooth muscle cells in GI tract
relax
what does ACh do to smooth muscle cells in GI tract
contract
direction of food movement in GI tract
unidirectional
what nervous control increases GI motility
parasympathetic nerve activation
what nervous control decreases GI motility
sympathetic nerve activation (NA)
how does sympathetic nerve activation decrease GI motility
directly via beta adrenoceptors and indirectly by decreasing ACh release via alpha-2 adrenoceptors
stages of GI motility
mastication (oropharyngeal) and deglutition (oesophageal)n
what is the role of zones of elevated pressure (ZEP) in the GI tract
prevent transit from one region to another (eg backflow)
how is peristalsis initiated
mechanoreceptors in pharynx detect food bolus which initiates peristaltic wave controlled by vagal nerves (gravity assisted)
what controls GI tract smooth muscle excitability
myogenic properties of smooth muscle cells
activity of intrinsic nerves
activity of extrinsic nerves
hormones or locally produced chemicals
when can BER from the GI pacemaker cells cause a peristaltic wave
when underlying smooth muscle is at it's most excitable and is able to reach the threshold potential
why are peristaltic waves weak for the first hour after eating food
to allow gastric contents to mix and make room for the food bolus
how is relaxation in corpus and fundus induced
by vagal relaxation fibres stimulated by oesophageal and gastric distension which is mediated by VIP
stimulatory GI tract motility hormones
gastrin (antrum) and motility (small intestine)
inhibitory GI tract motility hormones
gastrin (proximal stomach), secretin, CCK, NO
how does the meal composition of food eaten affect GI tract motility
larger food volume increases rate of gastric emptying
size of fragments of food
osmolarity (greater or smaller than 200mOsm slows rate of emptying)
excess acid slows gastric emptying
more fat slows gastric emptying
2 types of contraction in small intestine
segmenting and peristaltic
describe segmenting contraction in the small intestine
occurs in circular muscle and move chyme to and fro to increase exposure to mucosal surface
describe peristaltic contraction in the small intestine
occurs in longitudinal muscle over short distances after a meal
describe migrating motility complex (MMC)
occasional propulsive movement propagating over long distances (peristaltic contractions)
what is the role of ileal-caecal sphincter (ZEP) in the large intestine
prevent retrograde movement of bacteria from the colon during movement of chyme
describe the movement of the large intestine during digestion
slow and non-propulsive (Haustral contractions) to knead contents (similar to segmentation in SI)
describe movement of faeces out of the rectum
arrival of faecal material stimulates sensory nerves
causes peristaltic wave in colon
internal anal sphincter relaxes
how is faeces held in by the anus
external sphincter of anus has voluntary control
how does straining increase defecation volume
increases intra-abdominal pressure on colonic and rectal walls
what will a change in absorption effect (AUC, Tmax, F, V, CL, T1/2)
AUC, Tmax, F (only t1/2 if absorption greatly prolonged)
what will a change in distribution effect (AUC, Tmax, F, V, CL, T1/2)
V, T1/2
what will a change in elimination effect (AUC, Tmax, F, V, CL, T1/2)
AUC, CL, T1/2
what effects rate of passive diffusion
concentration gradient across membrane
surface area
membrane thickness
lipid solubility
molecule size
why do charged drugs need to become uncharged
only uncharged drugs can cross cell membrane
how do you find the pKa (ionisation constant) of a drug
pH at which drug is 50% charged and 50% uncharged
are weak base drugs more charged or more uncharged in a decreased pH (more acidic)
more charged
are weak acid drugs more or more uncharged in a decreased pH (more acidic)
more uncharged
are weak acid or weak base drugs better for absorption in stomach and intestine and entry into the brain
weak base drugs
do weak acid or weak base drugs have better absorption in the stomach
weak acids
why are weak acid drugs easily absorbed by the stomach
A- + H+ = HA (HA can be absorbed as its uncharged)
why do some drugs need to be taken with food
takes longer for drug to be absorbed
describe acid stable drugs
slower absorption in stomach
describe acid labile drugs
stays in stomach for longer and is more easily broken down
are acid stable or acid labile drugs taken with food normally
acid labile
define human microbiome
all microorganisms that live on or in the body forming a dynamic and interactive microecosystem crucial for maintaining health
main locations on body of human microbiomes
skin, mouth, lungs, GI tract, eye, hair follicles, nasopharyngeal, genital tract (male and female)
normal processes that can be affected by the human microbiome
body weight, mood, cholesterol level, sleep, vitamin absorption, cancer, blood pressure, response to drugs,
factors influencing microbiome diversity
living environment, drugs, birth mode, diet, immune disease, metabolic disease, colorectal cancer, autism, age
factors leading to opportunistic infection
compromised immunity, antibiotic suppression of normal flora, breach of physical barriers, impaired normal clearance mechanisms (smoking impairing cilia)
how can lipid soluble drugs be excreted
metabolised by liver, gut or blood to become a water soluble metabolite which can be excreted by the liver or kidney
how are volatile drugs (eg anaesthetics) excreted
via lungs
examples of drugs inactivated by metabolism
warfarin, phenytoin
examples of drugs activated by metabolism (prodrugs)
clopidogrel, codeine
timeline of paracetamol overdose
paracetamol metabolised
10% metabolism by CYP
metabolism by these creates NAPQI which is a toxic metabolite
metabolite has toxic reactions with proteins and nucleic acids which can lead to liver failure
antidote for paracetamol overdose
N-acetylcysteine
what occurs during phase 1 of drug metabolism
introduction/unmasking of functional group which somewhat increases water solubility using cytochrome P450
what occurs during phase 2 of drug metabolism
conjugation with endogenous chemical at functional centre which gives a great increase in water solubility
Non-viral causes of hepatitis
leptospirosis, brucellosis
preicteric clinical features of acute viral hepatitis
malaise, anorexia, nausea, abdominal discomfort, pyrexia (fever)
interim clinical features of acute viral hepatitis
pale stool, dark urine, jaundice
describe the hepatitis A virus
RNA genome
positive single strand
entry via contaminated food or water
excreted in faeces
consequences of hepatitis A
asymptomatic infection (worse as adult)
acute icteric hepatitis
fulminant hepatitis (rare)
prevention of hepatitis A
care with food and water, vaccination (whole killed virus)
describe the DNA of hepatitis B viruses
partially double stranded (one circular DNA and a partial second strand) (hepadnavirus)
envelope of hepatitis A vs B
hepatitis A has no envelope
outcomes of acute hepatitis B infection
subclinical infection
acute icteric hepatitis
fulminant hepatitis
chronic infection (10%)
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