1.03 Medical Sciences

what is one unit of alcohol?

8 grams/10ml

how do you calculate alcohol units?

alcohol percentage (ABV) x volume (ml) / 1000

what are the NHS recommended limits of alcohol consumption?

no more than 14 units per week (but spread out over at least 3 days)

how can alcohol enter the body?

- Ingestion

(slowly absorbed from the stomach & quickly absorbed from small intestine)

- nasal passage

- lungs

- skin

- other epithelia

how many calories per gram in ethanol?

7 calories per gram

is ethanol water soluble?

no, so it does not enter fat

what can affect the uptake of ethanol?

- size and body build (women have a higher relative fat percentage and lower water content = higher concentration in blood)

- the alcohol type and concentration

- faster uptake with carbonated alcohol

- greater effect with an empty stomach

- uptake increased by drugs that enhance gastric emptying and drugs that inhibit gastric alcohol dehydrogenase

- delayed by food (especially carbohydrates)

- caffeine counters alcohols soporific (sleeping) effects

how is alcohol distributed in the body?

- throughout the water in the body

- most tissues are exposed to same conc of alcohol in the blood

- exposure for the liver is greater because blood is received directly from the small intestine via the hepatic portal vein

how quickly does alcohol diffuse?

fairly slowly into the tissues, except from organs with a rich blood supply e.g. brain and lungs

what are the short-term physiological effects of alcohol?

mouth - slurred/confused speech

stomach + oesophagus - nausea, vomiting, heartburn gastritis

intestines - diarrhoea

pancreas + sugar digestion - pancreatitis + hyperglycaemia

kidney + fluid balance - dehydration + depleted salts + minerals

heart + blood pressure - tachycardia, arrythmias and increases in blood pressure

brain + nervous system - impaired concentration, memory loss, coma

- sweating, flushing and bruising

- body is at increased risk of rapid heat loss and hypothermia

what are the long-term effects of alcohol? (7)

mouth - cancer of mouth, larynx, throat

oesophagus - cancer

stomach - chronic gastritis

intestines - bowel cancer

liver - cancer, alcoholic liver disease

pancreas + sugar digestion - acute and chronic pancreatitis

heart + blood pressure - coronary heart disease, hypertension, heart failure due to cardiomyopathy

blood + immune system - anaemia, hepatitis C, TB, infections

lungs - pneumonia

brain + nervous system - brain damage (Wernicke's, Korsakoff, nerve damage, epilepsy, sleep disturbances, stroke

mental health - addiction/dependence, mood disorders, withdrawal symptoms

what is Wernicke's encephalopathy?

- from chronic excessive alcohol consumption

- leads to thiamine (vitamin B1) deficiency

- causes brain tissue ischaemia + death

what are the signs of Wernicke's encephalopathy? (3)

- acute confusion

- opthalmoplegia

- ataxia

what is opthalmoplegia?

paralysis of the extraocular muscles

how do you treat Wernicke's encephalopathy?

Pabrinex IV (thiamine replacement)

what does Wernicke's encephalopathy lead to if untreated?

Korsakoff's psychosis

what is Korsakoff's psychosis?

irreversible amnesic disorder

what are the signs for Korsakoff's?

- amnesia (anterograde + retrograde)

- psychosis

- confabulation

what is anterograde amnesia?

cannot form new memories

what is retrograde amnesia?

cannot remember old memories prior to brain damage

what is confabulation?

fabricating events to fill in memory gaps

what causes increased blood pressure and heart rate?

stimulation of hypothalamus

what causes dehydration?

kidneys secrete more urine due to osmotic effect of alcohol and inhibition of anti-diuretic hormone

what are the 2 mechanisms for alcohol metabolism?

- oxidative metabolism

- microsomal ethanol-oxidising system (MEOS)

what is the first step in oxidative alcohol metabolism?

- takes place in the hepatocytes

- ethanol is oxidised to acetaldehyde, which is catalysed by ADH (alcohol dehydrogenase found in cytosol) containing coenzyme NAD+

- ethanol ----ADH----> acetaldehyde

- CH₃+OH ---> CH₃CHO

- NAD+ ---> NADH - NAD+ is reduced

what is the second step in oxidative alcohol metabolism?

- in the mitochondria

- acetaldehyde is converted to acetate by ALDH (acetaldehyde dehydrogenase found in mitochondria)

- also results in NAD+ ---> NADH

what is NADH?

an electron transporter that enables oxidative phosphorylation to take place in mitochondria

what is the third step in oxidative alcohol metabolism?

- acetate is further oxidized in mitochondrial extrahepatic oxidation to CO₂ and water through the citric acid cycle

- acetate entering citric acid cycle generates more NADH

what happens in the microsomal ethanol-oxidising system (MEOS)?

ethanol converted to acetaldehyde by cytochrome P450 enzyme

when does the MEOS occur instead of oxidative metabolism?

chronic alcohol consumption

what is the metabolism of alcohol like in heavy drinkers?

- faster metabolsim

- high blood acetate levels

- lots of microsomal ethanol oxidising system

- dependent on a live chromosome

- uses NADPH to produce NADP+ by using ATP

- enzyme induction produced by drugs metabolised by the liver

what is the effect of alcohol on body temperature?

- it warms people up for a short amount of time

- rapid NADH production from alcohol metabolism increases energy availability and body temperature

- however risk of hypothermia

what metabolic processes are disrupted by alcohol and why?

- the oxidation of alcohol uses up a lot of energy so can inhibit metabolism of other nutrients

1) converts pyruvic acid to lactic acid

- hepatic gluconeogenesis inhibited so risk of hypoglycaemia

- overproduction of lactic acid blocks uric acid excretion of kidneys so risk of acidosis

2) inhibits lipolysis and increases lipogenesis

- too many fatty acids converted to ketones & lipids so leads to weight gain and ketosis

3) makes excess ATP

- inhibits fat oxidation leads to excess fat in liver and blood (and myocardial infarction)

how does alcohol damage the GI tract?

- inflammation of tongue, stomach, pancreas, liver and intestines

- alcohol metabolism leads to fat deposition, fibrosis and scarring of liver

- acetaldehyde interferes with absorption & activation of vitamins

- affects metabolism of drugs

- motility problems e.g. diarrhoea

what is ASH?

alcoholic steato hepatitis (ash)

- inflammation causes accumulation of extracellular matrix (collagen) from hepatic stellate cells

- leads to liver fibrosis

- scar tissue, and in severe cases can be fatal but can be reversed

what is cirrhosis of liver?

growth of connective tissue destroys liver cells with irreversible damage

what are the effects of alcohol intoxication?

- elation, euphoria, stimulation of pleasure & reward centres brain

- altered behaviour

- sedation (as it is a mild anaesthetic)

- after effects include insomnia, tiredness, nausea and headaches

what are the effects of alcohol on the brain?

- increases dopamine release -> euphoria

- inhibits glutamate receptor function -> amnesia

- potentiates GABA-A receptor function -> this is an inhibitory neurotransmitter in the brain

- increases serotonin release -> sleepiness

what are the 2 different components of pancreatic secretions?

- enzymatic

- aqueous

which enzymes does the pancreas produce?

- protease

- amylase

- lipase

which enzymes are secreted in active form?

lipases and amylase

which enzymes are secreted in an inactive form?

proteases

which cells secrete enzymes?

acinar cells

how do acinar cells secrete enzymes? (4)

- synthesised on RER and modified by golgi body

- placed in zymogen granules

- secreted upon stimulation by CCK

- granules leave by exocytosis

which cells release aqueous secretions?

ductal cells

what happens to pancreatic juice composition when flow rate increases?

- Na+ and K+ stays same

- Cl- decreases

- HCO3- increases

what happens to pancreatic juice composition when flow rate decreases?

- Na+ and K+ stays same

- Cl- increases

- HCO3 - decreases

which cell is involved in pancreatic enzyme secretion stimulation?

I cells

what stimulates I cells? (2)

small peptides and fatty acids

what do I cells do?

secrete CCK

what does CCK do?

- stimulate gallbladder contraction

- stimulate pancreatic enzyme secretion

what cell is involved in pancreatic aqueous secretion stimulation?

S cells

what stimulates S cells?

H+

what do S cells do?

secrete secretin

what does secretin do?

stimulates aqueous secretions of pancreas (ductal cells)

what 3 things does the liver store?

- carbohydrates

- vitamins

- minerals

how does the liver store carbohydrates?

as glycogen

how is glycogen synthesised? (4)

- glucose -> G6P by glucokinase

- G6P -> G1P by phosphoglucomutase

- G1P -> UDP-glucose by UDP-glucose pyrophosphorylase

- UDP-glucose added to glycogen chain by glycogen synthase

which vitamins are stored in the liver?

lipid soluble vitamins:

- A

- D

- E

- K

and vitamin B12

what mineral is stored in the liver?

iron

how is iron stored in the liver?

as ferritin

what substances can the liver synthesise?

- bile salts

- albumin

- clotting factors

- lipoproteins

what does the liver do in terms of detoxification?

- conversion of ammonia to urea

- phagocytosis

- drug metabolism

- alcohol metabolism

what role does the liver play in terms of bilirubin?

excretion of bilirubin

where does bilirubin come from?

product of macrophage destruction of haem molecules

what is the intermediate between haem and bilirubin?

biliverdin

what form is bilirubin initially in?

uncojugated bilirubin

what is the solubility of uncojugated bilirubin?

its lipid-soluble but not water-soluble

how does unconjugated bilirubin travel in the bloodstream?

binds to albumin

where does the unconjugated bilirubin and albumin travel to?

the liver

what does the liver do to unconjugated bilirubin?

hepatocytes conjugate it with glucaronic acid to make it water soluble

where does newly conjugated bilirubin go?

into the biliary system, it is secreted with bile

what happens to conjugated bilirubin in the intestines?

converted to urobilinogen by gut bacteria

what happens to urobilinogen? (2)

either:

90% - converted to stercobilin and excreted as faeces

10% - reabsorbed and excreted via kidneys as urine

what is the major vessel of the portal system?

the portal vein

what forms the portal vein?

the union of the:

- splenic vein

- superior mesenteric vein

where does union forming the portal vein happen?

posterior to the neck of the pancreas level L2

where does the portal vein go after the union?

ascends to the liver passing the superior part of duodenum and bile duct posteriorly

what happens just before the portal vein enters the liver?

it divides into left and right branches

what other smaller tributaries join to form the portal vein? (3)

- right and left gastric veins

- cystic veins

- para-umblical veins

what do the para-umbillical veins do?

drain the skin of the umbilical region

what tributaries make up the splenic vein? (4)

- short gastric veins

- left gastro-omental vein

- pancreatic veins

- inferior mesenteric vein (has its own tributaries)

what tributaries make up the inferior mesenteric vein? (3)

- superior rectal vein

- sigmoid veins

- left colic veins

what tributaries make up the superior mesenteric vein? (7)

- right gastro-omental vein

- anterior and posterior inferior pancreaticoduodenal veins

- jejunal vein

- ileal vein

- ileocolic vein

- right colic vein

- middle colic vein

draw a rough diagram of the portal venous system

what is metabolism?

sum of all chemical reactions in the body

what is catabolism?

breaking down fuel into simple molecules

what is anabolism?

building up complex molecules

what are the digestive products of carbohydrates?

- monomer sugars (fructose, glucose and galactose)

- disaccharides (maltose and lactose)

what 3 things are blood glucose dependent on?

- glucose absorption from intestine

- glucose production by liver

- glucose uptake and metabolism by all tissues in body

how much hepatic glycogen is stored in the liver?

50-100g

how long does the hepatic glycogen last?

maintains blood glucose for up to a 12-24 hour fast

what is glycogenolysis?

the breakdown of glycogen to glucose via phosphorylation

when does gylcogenolysis in the liver occur?

- when there is a fall in blood glucose concentration

- very important for providing glucose to brain and erythrocytes between meals

what stimulates glycogenolysis?

glucagon and adrenaline

what inhibits glycogenolysis?

insulin

what 4 enzymes are involved in glycogenolysis?

- glycogen phosphorylase - breaks long chains of glucose molecules

- debranching enzyme - removes branches

- phosphoglucomutase - converts G1P to G6P

- glucose-6-phosphotase - coverts G6P to glucose

whats the first step in glycogenolysis?

- removal of terminal glucose by breaking the α1-4 bonds using glycogen phosphorylase or a debranching enzyme

- this releases G1P

what is the second step of glycogenolysis?

- G1P is converted into G6P by enzyme phosphoglucomutase

what is the third step of glycogenolysis?

- G6P is converted to glucose by glucose-6-phosphotase

- glucose is transported out of the cell by GLUT2 straight into the bloodstream