S4C3 Flashcards
What us the cage questionnaire?
The CAGE is a simple screening questionnaire to identify potential problems with alcohol. “CAGE” is an acronym formed from the questionnaire (cut - annoyed - guilty - eye opener).
Two “yes” responses is considered positive for males
one “yes” is considered positive for females
What are the questions in CAGE?
- Have you ever felt you should Cut down on your drinking?
- Have people Annoyed you by criticising your drinking?
- Have you ever felt bad or Guilty about your drinking?
- Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (Eye-opener)?
What is ALT?
An enzyme found in your liver and kidney and is released into the blood when the liver is damaged
What is ALP?
An enzyme found in your liver and bones, increased in response to cholestasis
What is bilirubin? (brief)
Product of the breakdown of red blood cells and is excreted by the liver. High levels causes jaundice
What does high ESR show?
Inflammatory activity
How much ethanol is in 1 unit of alcohol?
8g of pure ethanol
What is Beck’s calculation?
Unit = amount (ml) x ABV
What is the pathway of alcohol?
Mouth + Oesophagus - Alcohol is diluted by saliva before being swallowed, Some is immediately absorbed
Stomach - More alcohol is absorbed here - leading to irritating the lining of the stomach and increasing the acidity
Small Intestine - Any remaining alcohol is passes here and is the site of the most alcohol absorption
Blood stream - Alcohol quickly diffuses through the body, affecting almost all cells
Brain - These cells are more susceptible because they are usually protected from toxins by the bbb
Liver - Blood-alcohol is metabolized in two stages and the respired into CO2. H2O and fatty acids
Excretion via urine, the lungs and sweat
What are the general effects of alcohol?
Stimulant at low levels
CNS depressant at moderate to severe doses
What does an acute administration of alcohol lead to?
Increase inhibitory transmission at gamma-amino-butyric acid (GABA-A) channels Increase serotonin (5HT-3)function Increased dopamine release Increased transmission at opiate receptors reduction of excitatory transmission at the NMDA subtype of the glutamate receptor
What are the bad social effects of alcohol?
Unwanted pregnancy
STDs
Cause of road traffic accidents
Major cause of domestic, football and other violence
What are the bad physical effects of alcohol?
Foetal alcohol syndrome Increase risk of oral/head/neck cancers Alcoholic cardiomyopathy Systemic hypertension Peripheral neuropathy CNS e.g. Korsakoff' psychosis, Wernicke's encephalopathy Withdrawal syndromes Alcohol poisoning Affect GI tract
What are the symptoms of alcohol poisoning?
Confusion Loss of coordination Vomiting Seizures Irregular or slow breathing (<8 breath/min) Blue or pale skin Hypothermia Stupor - conscious but unresponsive Unconsciousness
What is the affect of alcohol on the oesophagus?
Carcinoma of oesophagus, especially squamous carcinoma
Oesophageal varices, associated with chronic liver disease
What is the affect of alcohol on the Stomach?
Acute gastritis
Acute ulceration
Chronic peptic ulceration
Portal gastropathy
What is the affect of alcohol on the Pancreas?
Acute pancreatitis
Chronic pancreatitis
What is the basic normal function of the Liver?
Protein synthesis - albumin, clotting factors
Glycogen storage
Deamination
Detoxification of xenobiotics, hormones, ingested drugs
Bilirubin metabolism
What are the stages of alcoholic liver disease?
Acute fatty Change
Alcoholic hepatitis
Hepatic fibrosis
Describe the acute fatty change stage
Predominantly acinar zone 3
Mainly large droplet - macrovesicular
May cause acute hepatic failure
Describe the Alcoholic hepatitis stage
Mallory’s hyaline
Intracytoplasmic accumulation of keratin
Associated neutrophil polymorph infiltration
Describe the hepatic fibrosis stage
Starts in acinar zone 3
Initially pericellular fibrosis
Caused by activation of hepatic stellate (Ito) cell
Facultative myofibroblast
Leads to Cirrhosis which is irreversible and potentially to a Hepatocellular carcinoma
What are the mechanisms for Alcohol related disease?
Direct toxic effect
Indirect metabolite effect - Acetaldehyde
Activation of free radicals
Induction of enzyme systems - Cytochrome p450
Nutritional deficiencies esp. B group vitamins Liver function impairment
What does the GMC say about respecting patients?
You must not use your professional position to pursue a sexual or improper emotional relationship with a patient or someone close to them.
You must not express your personal beliefs (including political, religious and moral beliefs) to patients in ways that exploit their vulnerability or are likely to cause them distress.
You must be open and honest with patients if things go wrong. If a patient under your care has suffered harm or distress, you should:
1. put matters right (if that is possible)
2. offer an apology
3. explain fully and promptly what has happened and the likely short-term and long-term effect
What is the PRIME theory of motivation?
1: It is wants and needs at each moment that drive our behaviour.
2: Our intentions and beliefs about what is good or bad only influence our actions if they create sufficiently strong wants and needs at the relevant moment.
3: Our image our ourselves and how we feel about that, our identity, is a potentially very strong source of wants and needs which can be enough to overcome ones arising from biological drives such as hunger.
What is the self-regulation model?
The planful action designed to change the course of one’s behaviour
The executive capacity to plan, guide and monitor ones behaviour flexibly according to changing circumstances
Addictive behaviours are seen as the result of having an excessive reliance on external structures
It is important in the development of drug use problems
What is the Cue exposure theory?
Classic conditioning Plays part in development and maintenance of addictive behaviours A cue that has been present when drugs were administered is more likely to elicit a conditioned response 2 types of cue Exteroceptive - occur before use Smell of alcohol Sight of needle Time of day Interoceptive Effects of receptors Mood cues
What causes Diarrhoea ?
Increased osmotic load in colon increases fluid in faeces
Osmotic load - incomplete digestion and absorption of food
Lack of enzymes or transporters
Damage to mucosal cells
Osmotic load - secretion of ions by gut
What can cause a lack of enzyme or transporters?
Congenital (neonate) = "Watery" SGLT1 mutations Lactase deficiency Disease of pancreas and biliary systems - stratorrhoea Pancreatitis CF Hepatitis Gall stones
What can cause damage to mucosal cells?
Immune/ autoimmune
Coeliac disease
Crohn's disease
Infections (water and hygiene)
Bacteria
Shigella and Campylobacter cause destruction of intestinal wall - Decreases surface area + Blood in faeces (dysentery)
Salmonella causes inflammation
Protozoa (giardia or Entamoeba)
UK main causes are rotavirus and norovirusHow do some bacteria effect the secretions of ions by gut?
Toxin produced by bacteria which “hi-jacks” normal cellular processes
Intestinal cells normally secrete H2O (together with mucus and HCO3-) ~1L/ day
In cholera secretion exceeds 20 L per day
Toxins may also inhibit Na+ absorption but no SGLT1 - Basis of oral rehydration therapy
What is glucose-galactose malabsorption syndrome?
Genetic disease
SGLT1 mutated - no absorption of glucose or galactose
Severe and potentially fatal diarrhoea in infants
Treatment: to avoid glucose and galactose
How can genetic diseases cause mild malabsorption?
B0 - hartnup disease
B0+ causes cystinuria and kidney stones
What are the 3 ways of absorption?
simple diffusion - lipids
carrier-mediated - amino acids and sugar
Secondary active
Facilitated diffusion
Receptor-mediated endocytosis
Vit B12 + intrinsic factor
CholesterolWhere can digestion of proteins occur?
Stomach, pancreas, brush border
Where can digestion of polysaccharides occur?
Saliva, pancreas, brush border
Where can digestion of triglycerides occur?
Stomach, pancreas, bile salts
What are the different sites of absorption and what do they do?
Mouth, oesophagus and stomach - limited diffusion
Duodenum and jejunum - Major site
Ileum - Vit B12, Bile salts and K+
Colon - Na+, H2O and short-cahin fatty acids
Rectum - limited diffusion
What are the features of the small intestine allowing absorption?
Expansion of absorptive surface
Total area ~200m2
A decrease in surface area can lead to Malabsorption
Polarised expression of transport proteins
How are glucose
and galactose absorbed?
Secondary active transport - energy derived from Na+ gradient created by Na+K+ pump.
3Na+ is pumped out to interstitial fluid (2K+ pumped in)
Na+ gradient formed
Glu brought in with 2Na+ from lumen by SGLT1
GLUT2 then pumps glu into isf
How is fructose absorbed?
Facilitated diffusion
GLUT5 bring fruc in from lumen
GLUT2 pumps it into interstitial fluid
How many amino acids are absorbed by PEPT1? How does PEPT1 work?
50% absorbed as di-/tri- peptides
They become hydrolysed to aa in enterocyte.
Works by contransporting H+
How does Bo transport amino acids? What type of aa does it transport?
Neutral a.a
Co-transports Na+
How does Bo+ transport amino acids? What type of aa does it transport?
cationic and cystine
Co-transports Na+
How does Xag- transport amino acids? What type of aa does it transport?
Anionic a.a
Co-transports Na+ and H+, K+ pumped other direction
What aa does PAT1 transport?
Proline
How is fat digested?
Dependent on bile salts
Emulsification of large fat droplets - Increase surface area for action of pancreatic lipase
Formation of mixed micelles - Stabilises products of triacylglycerol hydrolysis (into monoacylglycerol and 2 free fatty acids) while they are translocated to apical membrane
How is fat absorbed?
Simple diffusion of Free fatty Acid - Limited with a few FFAs in undissociated state (pKa ~ 4.9)
FFA transporters - FAT plus CD36
Short-chain FA transporters in colon -Produced by bacterial fermentation
Monoacylglycerol transport -Evidence for carrier-mediated mechanisms
Triacylglycerol then gets re-synthesised in ER - Packaged in chylomicrons
How is cholesterol absorbed?
Duodenum
Niemann-Pick C1-Like1 (NPC1L1) protein
Receptor mediated endocytosis
Ezetimibe inhibits endocytosis - Decreases plasma cholesterol
How is H20 absorbed?
H20 moves down osmotic gradient
Osmotic gradient created by absorption of nutrients
8.4L absorbed in total per day
6.5L in small intestine, 1.9L in colon
Route:
Via junctional complexes between cells, Via SGLT1 And a.a. Transporters
How is Na+ absorbed in different parts of the GI tract?
In jejunum and ileum - Na/glucose or Na/aa cotransporters
In duodenum and jejunum - Na-H exchanger
In ileum and proximal colon - Parallel Na-H and Cl-HCO3 exchangers
Distal colon - epithelial Na+ channel
How and where is Cl- absorbed?
In ileum and proximal colon - Parallel Na-H and Cl-HCO3
How is HCO3- and K+ absorbed?
HCO3- –> no active absorption in Si or LI
K+
SI - paracellular diffusion in ileum
LI - predominantly secretion
How much HCO3- and K+ are in faeces? What happens in cases of severe diarrhoea?
K+ = 90mM
HCO3- = 30mM
Severe diarrhoea - hypokalaemia and metabolic acidosis
How are vitamins absorbed?
Fat soluble: A, D, E and K
Evidence of facilitated diffusion and/or endocytosis at physiological concentrations
Require optimal fat digestion
Deficiencies within pancreatic and biliary disease
Water soluble: B and C
Specific transporters (facilitated and secondary
B12 - endocytosis
How is Ca2+ absorbed?
Can be absorbed either paracellular or transcellular
Transcellular:
Ca2+ transported into the cell by TRPV6
Transported into interstitial space by PMCA (brings H+ in uses ATP)
How is nonheme Fe3+ absorbed?
Dcytb reduces Fe3+
DMT cotransports Fe2+ with H+
Fe2+ binds to mobilferrin
Fe2+ leaves the cell via Ferroportin and binds to transferrin in plasma after hephaestin oxidises
How is heme Fe2+ absorption?
Heme Fe2+ enters the cell
Heme oxygenase oxidises the Fe2+ and releases it
Fe2+ binds to mobilferrin
Fe2+ leaves the cell via Ferroportin and binds to transferrin in plasma after hephaestin oxidises
What is the cost of alcohol to society?
£11 billion - alcohol related crime
£7 billion - lost productivity through unemployment and sickness
£3.5 billion - cost to NHS
What are the health statistics for alcohol?
10.8 million adults in England are drinking at levels that pose some risk to their health
1.6 adults may have some level of alcohol dependence
Alcohol has been identified as a casual factor in over 60 medical conditions
333,014 hospital admission were alcohol related in 2013-2014
17,432 deaths from liver disease between 2011-2013 - 15% increase from 2002
150,640 receiving specialise treatment for alcohol dependence in 2014-2015 (60% problematic drinking, 40% alcohol alongside other substances)
What are the social factors which makes someone vulnerable to alcohol consumption?
Alcohol pricing, availability and regulation
Drinking context
Socio-economic statuc
Culture
What are the individual factors which makes someone vulnerable to alcohol consumption?
Mental health
Homelessness
Gender
Age
What is the pancreas?
A retroperitoneal organ, at the level of the transpyloric plane, located in the epigastrium and left hypochondrium regions.
Lobulated capsule organ with septa
The exocrine pancreas is classified as a lobulate, serous gland which produces digestive enzyme precursors.
How can the pancreas be divided?
Divided into 5 parts:
Head - the widest part of the pancreas
Lies within the C-shaped curve created by the duodenum
Connected to duodenum by connective tissue
Uncinate process - a projection arising from the lower part of the head
Extends medially to lie beneath the body of the pancreas
Lies posterior to the superior mesenteric vessels
Neck - located between the head and body
Overlies the superior mesenteric vessels which form a groove in its posterior aspect
Body - centrally located, crossing the midline of the human body to lie behind the stomach and to the left of the superior mesenteric vessels
Tail - lie within close proximity to the hilum of the spleen
Contained within the splenorenal ligament with the splenic vessels
Only part of the pancreas that is intraperitoneal
What is the duct system in the pancreas?
Acini are connected by short intercalated ducts
The intercalated ducts untie with those draining adjacent lobules and drain into a network of intralobular collecting ducts, which in turn drain into the main pancreatic duct
The main pancreatic duct runs the length of the pancreas and unites with the common bile duct
Forming the hepatopancreatic ampulla of Vater - This opens into the duodenum via the major duodenal papilla
Secretions in the duodenum are controlled by the sphincter of Oddi which surrounds the ampulla of Vater.
The accessory pancreatic duct opens into the duodenum at the summit of the minor duodenal papilla
What is the arterial supply of the pancreas?
Derived from branches of splenic artery
Multiple pancreatic arteries form several arcades with pancreatic branches of the gastroduodenal and superior mesenteric arteries
The anterior and posterior superior pancreaticoduodenal arteries, branches of the gastroduodenal artery, and the anterior and posterior inferior pancreaticoduodenal arteries, branches of the SMA, form anteriorly and posteriorly placed arcades that supply the head of the pancreas
What is the venous supply of the pancreas?
Via corresponding pancreatic veins, tributaries of the splenic and superior mesenteric parts of the hepatic portal vein
Most empty into the splenic vein
What is the lymphatics of the pancreas?
Most vessels end in the pancreaticosplenic lymph nodes which lie along the splenic artery
Some vessels may end in the pyloric lymph nodes
Efferent vessels from these nodes drain to the superior mesenteric lymph nodes or the celiac lymph nodes via the hepatic lymph nodes
What is the innervation of the pancreas?
Derived from the vagus and abdominopelvic splanchnic nerves passing through the diaphragm
What are the different endocrine cells in the pancreas? What do they secrete and what does that do?
β cells - insulin - increase blood glucose and satiety
α cells - glucagon - lowers blood glucose
δ cells - somatostatin - inhibits secretion of insulin and glucagon
ε cells - ghrelins - increase appetite
PP cells - pancreatic polypeptide - promotes GI fluid secretion and satiety
What are the components of pancreatic juice? Where are they produced and what controls them?
Bicarbonate (NaHCO3) in duct controlled by secretin
Enzymes - regulated by the vagal reflex and CCK in the acinus - also causes NaCl secretion
How does NICE make decisions on prioritising health care?
. NICE makes decisions based on the “accountability for reasonableness” conditions described above and lists scientific rigour, inclusiveness, transparency, independence, challenge, review, support for implementation, and timeliness as its key procedural principles
