GI clinical sessions Flashcards
what are the main functions of the liver
- cholesterol metabolism
- drug metabolism
- carbohydrate metabolism
- -FA metabolism
- NH3 metabolism
- protein synthesis
- bile formation
what are the 4 clinical problems we can get with the liver
acute hepatitis
chronic liver disease
extrahepatic billary obstruction
fatty liver disease
what is Hep A? how is it spread? how does it affect the liver
RNA virus
spread via the faecal-oral route
- causes hepatocyte necrosis and inflammation as it replicates in hepatocytes
what are the symptoms of hep A
jaundice dark urine (bilirubin metabolism is altered) pale stools malaise anorexia nausea abdominal pain
what are the clinical features of hep A
jaundice
hepatomegaly
splenomegaly
rash
what are the consequences of hep A
can cause relapsing hepatitis or cholestatic hepatitis (prolonged phase of jaundice) which can be recovered from
or acute liver disease which can lead to death if no liver transplant (v rare)
can people be asymptomatic with hepA
yes- for most people lines normally short and no treatment is required
what is chronic liver disease
a permeant and progressive pathological change throughput the liver (associated with repeat liver injury)
how does chronic liver disease effect the structure of the liver
changes the lobular architecture - portal tracts separated from portal viens
what can chronic liver disease lead to
fibrosis and cirrhosis
what are the causes of cirrhosis
alchohol fatty liver disease hep C and B primary billary cirrhosis auto immune liver disease
what are the morphological changes in cirrhosis
- hepatocytes damaged and function poorly
- sinusoidal/canalicular pathways disturbed
- disrupted intrahepatic biliary drainage
- disturbed vascular perfusion
what are the clinical effects of cirrhosis
- jaundice
- ascites
- encephalopathy (abnormal brian function)
- portal hypotension
- splenomegaly
- renal failure
- heptocelluar carcinoma
- bleeding tendency
how can portal hypertension cause renal failure
increased pressure in portal vein openes up channels in liver that are normally not needed leading to the liver becoming differ and the sinusoidal channels disrupted = blood flow in liver is disrupted and flows around the liver = urea and waste not removed
what are the symptoms of liver disease
jaundice anemia heptomegaly splenomegaly thin: muscle wasting liver palms clubbing dilated periumbical viens spider nevai
what are spider nevi
spider like marking on the skin
what characteristic is associated with portal hypertension
distended abdomen - larger than pregnancy
what are liver palms ? why do they happen
dilated hands- sex steroid hormones not verbalised and accumulate
what is billary obstruction ? what are the main causes ?
obstruction of the extraheptic billary system leading to decreased excretion of bile
commonly due to gallstones or pancreatic cancer
what is billary obstruction also known as
obstructive jaundice
what are the clinical effects of biliary obstruction
- jaundice
- dark urine
- pale stools
- itching
- steatorrhoea
- weight loss
- vit déficiences (lipid soluble ones:AKED)
- pain
- disturbed lipid metabolism
what can cause fatty liver disease
lots of things: alchohol drugs diabetes obesity
what is the metabolic syndrome? what is it also known as
also known as the deadly quartet :
- abdominal obesity
- hypertension
- diabetes mellitus
- dyslipidaemia
what is the 2 immunological cells in the liver and what are they involved in
kupfer cells- bacterial degradation
pit cells –> liver NK cells
what are the 3 most common causes of liver disease in the UK
viral hepatitis
alchohol consumption
Non alcoholic fatty liver disease : NAFLD)
what is viral hepatitis
liver inflammation
what is the least serious type of Hepatitis
Hep A
do people normally become chronically affected with hep A
no usually resolves within a few weeks
which type of hepatitis mainly causes chronic liver disease
Hep B
(usually no acute hepatitis but can remain chronically affected for their lifetimes )
Hep C
what are the symptoms of Hep B
similar to Hep A but fever more common
also many include:
raises, pain and polyarhritjs
what is polyarthritis
swelling of the joints
do individuals recover form hep B
yes usually full revcovery made, however 1-5% patients remain chronically affected
what can chronic infection of Hep B lead to
cirrhosis and liver cancer (hepatocellular carcinoma- HCC)
do symptoms start early for Hep B
no usually patients dont know they have been effected in the early stages
what does the treatment of Hep B involve
48 week course of Pegylated interferon injection administered weekly
or oral antiviral agens - Tenofovir to supress levels of virus
what kind of infection does Hep C involve (acute or chronic?)
usually asymptomatic acute infection and 70-80% develop chronic infection , remaining asymptotic
when is Hep C usually diagnosed
when patients present with chronic liver disease years after original infection
how is Hep C usually transmitted
usually by blood to blood products (therefore in drug users)
also common in patents with haemophilia
does Hep B or C carry a better chance of cure
Hep C - successful treatment prevent progression of liver disease
which Hep is the commost common in the UK
Hep E
how can Hep E be transmitted
via faecal-oral route or consumption of raw undercooked pork or shellfish
which individuals are most at risk of Hep E
those with underlying liver diseases or alcohol-related liver disease
what is the treatment for Hep E
normally resolves on own
what is alcoholic liver disease
inflammation (alcoholic hepatitis) and fatty acid accumulation (accumulation of triglycerides) in heptocytes
what are the long term effects of alcoholic liver disease
fibrosis or cirrhosis
why do we get fatty acid accumulation in alcoholic liver disease
decrease in fatty acid metabolism and increase in fatty acid synthesis
what are the risk factors for non alcoholic fatty liver disease (NAFLD)
hypertension
obesity
insulin resistance
type 2 diabetes
how does NAFLD affect the liver
fat accumulation can be associated with inflammation which may lead to fibrosis or cirrohsis
are patients with NAFLD usually asymptomatic or not?
usually asymptomatic until complications of liver disease and cirrhosis present (jaundice, ascites, bleeding, HCC)
in most. cases what does inflammation of the liver usually lead to ?
fibrosis and cirrhosis
describe the structural changes to the liver of cirrhotic patients on a cellular level
- micro nodular aperence (due to the regeneration )
- thick bands of collagen (scar tissue)
- cells swollen ( with fat droplets)
- mallory body (cytoplasms with denatures keratin)
what are inherited conditions that cause liver cirrhosis
- galactosaemic
- glycogen storage diseases
- Wilsons disease
how can immune mediated damage effect the liver
primary billary cirrhosis
how can bile duct damage effect the liver
bile accumulates and damages the liver and tissues = secondary billary cirrhosis
what is the difference between hepatitis and cirrhosis of the liver? are they reversible?
hepatitis = inflammation - reversible
cirrhosis = scarring = irreversible
what do you normally test for in a liver function test
albumin total bilirubin alkaline phosphatase alkaline transaminase aspartate transaminase y-glutamyl transferase
in liver disease are albumin levels high or low? what does this normally cause
low levels
can result in oedema and ascites
in liver disease are bilirubin levels high or low? what is this due to?
high
due to damage in the liver or bile duct blockage
high levels of billirbun causes…
jaundice
are levels of alkaline phosphatase in liver disease usually high or low ? why
high as released when cells are destroyed- from damaged bile ducts
are levels of alanine and aspartate transaminase in liver disease usually high or low ? why
high due to liver damage - enzymes are released when hepatocytes damaged
usually used to show ongoing liver damage
what does y-glutamyl transferase indicate in a LFT
induced by alcohol so can indicate early liver dysfunction
NOTE- not specific can be raised from drugs
other than a liver function test what other tests could you carry on on patients suspected for liver damage
imaging of the liver : ultrasound or biopsy
why might oesophageal varicies lead to the vommiting of blood
blood flow through varices - can burst - patient can bleed to death
why would oesophageal varicies develop
fibrosis of the liver can disrupt the portal vein increasing resistance so blood flow through other vessles in the oesophagus
why might someone with liver disease have itchy skin
accumulation of bile salts in skin = irritation
why might someone with liver disease have steatorrhoea
due to pancreatitis which occurs with increased alcohol use = lipase not released = fat not broken down
why might someone with liver disease have more bruising and bleeding
lack of synthesis of clotting factors and Vit K
why might heavy drinkers be hypoglycemic.
liver damage = less hepatocytes = cant store glucose as well or carry out gluconeogensis
Why are patients with liver disease always given an i.v. injection of thiamine (vitamin B1) before
administration of glucose
because B1 is a cofactor for pyruvate dehydrogenase involved to allow pyruvate to enter the Krebs
how can lack of B1 lead to WKS
without B1 pyruvate turn to lactate leading to lactic acidosis and neurological damage =WKS
Why should alcohol be consumed with caution when taking other drugs?
competition between alchohol and drugs for cytochrome P450 enzymes and so slower clearance of both substances = increasing side effects from both
what drugs should not be taken with alcohol
antihistamines
NSAIDS
antibiotics
antidepressants
why might heavy drinkers beed increased dosage of prescribed drugs
because high levels of CYP450 enzymes always present so you have increased metabolism of drugs
what drugs can decrease withdrawal symptoms of alcohol
chlordiazepoxide
chlorometriozole
diazepam
what does disulphiram do
inhibits the action of aldehyde dehydrogenase making person feel ill to drink
what treatments are given to patients with severely damaged livers
diruretics - oedema antibiotics - infections b blockers -portal hypertension clotting agents - internal bleeds liver transplant if v sevre
what does ‘dys’ and what does ‘pepsis’ mean in latin
dys = bad pepsis = digestion
= dyspepsia = indigestion
what are the 4 different types of dyspepsia
- dyspepsia with alarm symptoms (with red flag features)
- uncomplicated/ simple dyspepsia (dyspepsia without ‘red flag’ features)
- uninvestigated dyspepsia (dyspepsia presenting to physician for the first time)
- functional (‘non-ulcer’)
dyspepsia (have symptoms of dyspepsia but no evidence on endoscopy)
what are alarm features for dyspepsia
- weigh loss
- dysphagia : difficultly swallowing
- odynophagia : pain when swallowing
- haematemesis : vomiting blood
- melaena : dark poo, upper GI bleeding
- palpable epigastric mass
- family history of gastric cancer
- over 45-55 years
what are potential causes of dyspepsia
- gastro-oesophageal reflex
- peptic ulcer
- gastric cancer
which type of dyspepsia is most common ? why
functional dyspepsia due to a normal endoscopy
why would you perform a urgent GI endoscopy
if a patient presents with alarm symptoms
what is GI endoscopy poor in predicting
GI cancer
what are the strategies for managing dyspepsia
- endoscopy
- test for H.pylori
- empirical PPI (proton pump inhibitors)
what is the problem with endoscopy
v expensive on NHS , not cost effective
symptoms and signs of peptic ulcer?
epigastric pain
- epigastric tenderness
- nausea
- anorexia
- weight loss
in a peptic ulcer when does the epigastric pain present ? how can it be relieved
- after eating
- antacids, eating, drinking milk
what are the causes of peptic ulcers
*H.pylori *
non-steroidals/NSAIDS: aspirin, ibuprofen
Zollinger-ellison syndromes
Crohn’s disease
what is Zollinger-Elison syndrome
too much gastric acid production due to tumour cells in pancreas
what does H.pylori cause
gastric and duodenal ulcers
gastric cancer
how does H.pylori create an environment to enable to it survive
bacterium produces urease —> converts urea to NH3 anf H20 —> cloud of ammonia neutralises gastric acid pH in stomach = damages gastric linning (gastritis) and causes ulceration = it can survive
what methods can we use to diagnose for H.Pylori
- carbon urea breathe test
- H.Pylori serology (blood test)
- H.pylori stool antigen
invasive: done at time of endoscopy
- rapid urease test
- histological examinations of biopsy
what would you tyts for in a H.Pylori serology (blood test)
IgG - once have H.Pylori will always have the antibodies present
how do we treat patients with H.Pylori (ie. gastric ulcer/cancer, functional dyspepsia)
PPI- proton pump inhibitor and 2 ANTIBIOTICS: -amoxicillin -clarithromycin -metronidazole
what are the complications of peptic ulcers
- perforation (GI contents leak into peritoneal cavity:peritinitis )
- haemorrhage - bleeding (haemteasis, maleana)
- gastric outlet obstruction (pyloric stenosis)
how does gastric outlet obstruction (pyloric stenosis) presents
- persistant abdominal pain and discomfort
- massive somtach (food and build builds up)
how would you treat perforation or pyloric stenosis
surgery
how would you treat a bleeding ulcer
coagulation of bleeding point with adrenaline injections
if not work- heat probe
what are the symptoms and signs of a bleeding peptic ulcer
- haematemesis
- coffe-ground vomiting
- melaena
- rectal bleeding
- tachycardia
- hypotension
how does a peptic ulcer develop in the stomach/duodenum
break in the epithelial cells which penetrates to the muscularis mucosa
what is the difference between epigastric pain in stomach and duodenual ulcers
epigastric pain/ upper abdomen pain is worse at night in duodenal ulcers
what are the consequences of peritonitis caused by perforation of ulcers
sevre abdominal pain
shock
collapse
what kind of bacteria is H.Pylori
gram negative
what are the 2 strains of H.Pylori and how do they differ
CagA and VacA
- Cag A infects the epithelial cells, altering cell replication and leading to apoptosis
- VacA increases permeability of host cells and prevents stomal immune response so increases the ease of infection
how does H.pylori cause ulceration
causes infection and inflammation by increasing gastrin release and inhibiting somatostatin release
which blood group is at an increased risk of duodenal ulceration
blood group O
how do NSAIDS work
inhibit COX enzyme responsible for converting arachidonic acid into wide range of substances including prostaglandins
how might aspirin cause ulcers
inhibits prostoglands = more activation of parietal cells= increase gastric acid secretion
how many COX isoenzymes do we have
COX 1 (expressed all the time on gastric mucosa, kidneys, endothelial cells, platlets) and 2(expressed only in response to inflammation on monocytes and macrophages)
which COX isoenzyme is responsible for an inflammatory response and which is responsible for effects on gastric mucosa
COX 1 =effects on gastric mucosa
COX2 = inflammatory response
why might COX 2 specific NSAIDS be preferable to ibuprofen? what are the side effects of this?
more specific to inflammatory prostoglands not gastric mucosa prostoglands
however can increase clotting and constriction of capillaries leading to additional heart disease
why might aspirin promote haemorrhage from peptic ulcers
inhibits thromboxin formation = inhibiting blood clotting
what does a proton pump inhibitor inhibit
K+/H+ ATPase
other than PPI what other anti-ulcer drug can be used ? how do they work
H2 antagonists - prevent the binding of histamine one the H2 receptor = decrease acid release
why might someone with a haemorrhaged gastric ulcer become breathless and have a raised pulse but low BP
due to anaemia from blood loss
what abnormalities might someone with a haemorrhaged gastric ulcer have in their blood test
low Hb
high levels of urea (digestion of large amounts of RBC\
Does perforation or ulceration go through more layers
perforation
what is malabsorption
defective mucosal uptake and transport of adequately digested protein, fat, carbs, nutrients
disturbances to what 3 normal digestive functions leads to malabsorption
- intraluminal digestion (pancreatic enzyme secretion and emulsification by bile salts)
- terminal digestion (enzymatic hydrolysis in brush border of small intestine)
- trans-epithelial transport (nutrients, fluid and electrolytes transported across the epithelium)
why is absorption of electrolytes and nutrients paticulllary sodium important absorption ?
because all the water that is absorbed is absorbed via osmosis
what can a disturbance in electrolyte absorption lead to?
osmotic diarrhoea
what protein does cholera effect and how can it lead to watery diarrhoea
activates CFTR chloride channel and leads to large amounts of Na+, Cl-, and HCO3- secretion into lumen meaning water follows = watery diarrhoea
what 2 molecules are hydrolysed by brush border enzymes
starches: a-dextrins
peptides
what is lactose intolerance
defences in brush border enzymes (eg.lactase) = can lead to failure to breakdown disaccharides (eg.lactose) into glucose and galactose
how can lactose intolerance cause diarrhoea
disaccharides are not digested and remain in the gut so increases osmotic potential = draws more fluid into gut = diarrhoea
what is steatorrhea
presence of excess fat in faeces
what are the charcteriscts of steatorrhea
- stools may float in pan- hard to flush
- oil apprentice
- foul smelling
in what diseases do we see steatorrhoea
cholestatic liver disease
pancreatitis
coeliac disease
what is cholestatic liver disease
inadequate flow of bile
if fat absorption is impaired which vitamins will we see deficiencies in
A K E D
what is calcium absorption greatly reduced by
vit D deficiency
what can calcium malabosoprtion lead to
osteoporosis - reduced bone density
what are the causes for osteoporosis
anorexia smoking alcoholism malabsorption steroid therapy vit D or calcium defiancey
what is osteomalacia
normal amount of bone but the mineral content is low (poor quality- dense but soft)
what disease can lead to osteomalacia
ricks (if it happens during the period of bone growth)
what are the causes pf osteomalacia
- vit D deficiency
- malabsorption (coeliac, intestinal resection, cholestasis), renal disease
levels of which minerals does osteomalacia effect
- mildly decreased: calcium and phosphate
- increased: alkaline phosphate and parathyroid hormone
where is lit A mainly absorbed
small intestine
what can vitamin A deficiency cause
Xerophthalmia - eye problems
where is vitamin B12 absorption
small intestine
what can deficiencies in vitamin B12 lead to
angular stomatis (raw cuts around the mouth)
cheilitis (inflammation of the lips)
what is vitamin B1 also known as
thiamine
where is vitamin B1 absorbed
small intestine
what can deficiencies in vitamin B1 lead to
Beriberi and WKS
where is vitamin B6 absorbed
small intestine
what can deficiencies in vitamin B6 lead to
polyneuropathy
where is vitamin B12 absorbed
terminal ileum
what can deficiencies in vitamin B12 lead to
anemia
large RBC/macrocytic anemia
SCDC- degeneration of the spinal chord
where is vitamin C absorbed ? defines?
proximal ileum
scurvy
where is vitamin D absorbed? defines can lead to?
small intestine/skin
osteomalacia
where is vitamin E absorbed? defines can lead to?
small intestine
bleeding disorders
where is vitamin K absorbed? defines can lead to?
small intestine
bleeding disorders
how does vitamin B12 get absorbed
forms a complex with intrinsic factor in the stomach, facilitating its absorption —> absorbed in the terminal ileum
what diseases can lead to B12 defiency
- gastric mucosal atrophy
- terminal ideal disease
what does B12/folate control
the normal proliferation of cells - necessary for efficient thymidilate synthesis and production of DNA
where do we get our iron intake from
diet
where does iron normally get absorbed
duodenum
why might we get iron loss
bleeding
what is coeliac disease
inflammatory condition of the small intestinal mucosa produced by an autoimmune reaction to ingestion of gluten
how does coeliac disease effect the structure of the small intestine mucosa
villous atrophy - flat and blunted
intestinal inflammation
intraepithelial lymphocytosis
what is the clinical presentation of coeliac disease in infants
impaired growth
diarrhoea
vomiting
abdominal distension
what is the clinical presentation of coeliac disease in older children
anaemia short stature pubertal delay rickets recurrent abdominal pain behavioural disturbance
what is the clinical presentation of coeliac disease in adults
chronic anemia, diarrhoea, abdominal pian, bloating, nutritenial deficiencies, reduced fertility, osteoporosis, osteomalacia, abnormal Liver function tests
what can intestinal inflammation in coeliac disease lead to
intestinal transit = things move into gut v quickly
what does intestinal transit lead to
-decreased macronutrient absorption
-negative/calorie protein balance
= diarrhoea and weight loss
what can villous atrophy lead to
reduced surface area for absorption = decreased absorption of osmotically active substances = diarrhoea
what specific nutrient defences can occur in coeliac disease and what can they lead to
- iron/ folate –> anaemia
- calcium –> osteomalacia
- fat soluble vitamins AKED –> clotting disorders
how would you diagnose a patient for coeliac disease
- clinical history
- serological tests (for anti-tissue trnasglutaminase antibodies)
- duodenal biopsy via upper GI endoscopy
what is the management for coeliac disease
- gluten free diet
- replace nutritional deficneies (iron, calcium, folate, vit D)
- monitor bone density
- repeat small intestinal biopsy
is coeliac disease more common in men or women
women
what is parasthesia? why is it caused? what disease is it linked to
tingling in hands- caused by malabsorption of calcium
seen in coeliac disease
what is pancreatic insufficiency
reduced delivery of pancreatic enzymes to duodenum
in what diseases can we get pancreatic insufficiency
CF (reduced HCO3- and pancreatic fluid secretion ad blockage of ductus with mucous)
Chronic pancreatitis
what is chronic pancreatitis
irreversible glandular destruction and alteration of anatomy/ function due to chronic inflammation
what are the clinical features of chronic pancreatitis
- epigastric pain- often radiating towards the back - food or alcohol may exacerbate the pain
- wright los
what are the causes of chronic pancreatitis
alchohol familial congenital autoimmune genetic
what other disease is closely linked with chronic pancreatitis? why?
diabetes due to endocrine insufficiency
what investigations would you carry out for suspected chronic pancreatitis
- facael elastase-1 (produced by pancreas and passed into stool largley unaltered)
- abdominal X-ray
- ultrasound/CT
how do you manage chronic pancreatitis
- remove precipitant (eg.alchohol)
- pain control
- treat diabetes
- pancreatic enzyme supplemts (lipase, protease, amylase)
- vitamin supplements
what is cholestatic liver disease
impairment of bile formation of flow
what are the consequences of cholestatic liver disease
steatorrhoea
fat vitamin malabsorption
what is primary sclerosis cholangitis - PSC? what does it lead to
inflammatory/ fibrotic process affecting intra/extrahepatic bile ducts - type of cholestatic liver disease
leads to bile duct strictures (narrows bile ducts)
what is primary sclerosis cholangitis most commonly associated with
IBD
how does cholestatic liver disease (and PSC) present
- pruritus : itching as bile salts in skin
- fatigue
- jaundice
what does cholestatic liver disease (and PSC) lead to
cirrhosis and liver failure as bile can cause liver inflammation
what is the treatment for cholestatic liver disease (and PSC)
liver transplant
what is small bowel bacterial overgrowth to ? what is it normally seen with? how is it treated
bacteria degonjugate bile salts and metabolise B12
seen with structural abnormality (eg. Crohn’s)
rotating course of antibiotics
where are NA+/K+ ATPase normally found
all cells - distributed evenly on cell surface or clustered in membrane domains in basolateral membrane
how is Na rapidly excreted out of a cell? why is this importnant
sodium pumps - pumps it into intercellular spaces between adjacent enterocytes
establishes a high osmotic potential
how is sodium trnaprted into the cell
down its conc gradient alongside glucose and amino acids
or H+/Na+ antiport pump
how do chloride ions enter the cell
antiport Exchange with bicarbonate ions
how do we treat someone who is severely dehydrated form sevre diarrhoea
oral rehydration solutions containing water salts and glucose
why do oral rehydration solutions not only contain water
because the glucose and salts (Na and Cl) creates the osmotic gradient which is more negative allowing water to follow
what are the 2 processes which establish an osmotic gradient
- increase in luminal osmotic pressure from influx and digestion of foodstuffs
- crypt cells actively secreting electrolytes via their ion channels
what ion channel do crypt cells contain
CFTR
what 2 cells are villi mainly covered in
enterocytes and goblet cells
what cells are the crypts of leubrikun covered in
younger cells and stem cells (give rise to younger enterocytes which make their way up the villi as they mature)
highlight the process of water secretion across crypt cells
1- Na/K+ pump pumps sodium from cells = establishes Na gradient
2- symporter on basolateral surface transports Na, Cl, K into cell = secondary active transport via Na
3- CFTR activated from cAMP lead to Cl secretion
4- accumulation of Cl in crypt draws Na+ acrosss via tight junctions = secretion of NaCl
5- accumulation of NaCl creates transepithelial osmotic gradient drawing water across
what are the 3 main reasons we get malabsorption
- impaired digestion (pancreatic insifficnecy-CF, chronic pancreatisis)
- lack of bile
- lack of intestinal enzymes (lactose intolerance)
what are the 4 differnt types of diarrhoea
- osmotic: stuff in GI tract that cant be absorbed
- secretory : excess secretions into GI overwhelms ability to reabsorb fluid
- inflammatory : prevents absorption
- abnormal motility : chyme moving too rapidly through GI tract so absorption cant take place fully
why might we get bloating and flatulence from sugar
sugar is fermented by bacteria in large intestine producing acidic stools and gas
what are symptoms of lactose intolerance in a child
failure to gain weight
what are symptoms of lactose intolerance in an adult
- audible bowel sounds
- abdominal bloating
- flautulence
- nausea
- urge to defecate
- diarrhoea
- abdominal cramps
how do we diagnose for lactose intolerance
- eating dose of lactose and monitoring what happens in the 20-30 mins and whether the glucose levels go up (they shouldn’t)
- biopsy of small intestine to rule out coeliac disease
what is the treatment for lactose intolerance
avoid foods containing lactose
calcium suplements
what secretions are reduced in CF and why
pancreatic fluid and HCO3- due to blockage of ducts with mucous = preventing delivery from pancreas to duodenum (leading to steatorrhea)
what is meconium ileus
most common cause of CF in babies - disability of baby to pass first poop/meconium as pooop too thick and stickyyyyyyyy that it blocks the ileus
why do we get diarrhoea in adults with CF? what kind of diaoreha is this
osmotic diarrhoea
thickened mucus blocks the pancreatic duct = lack od digestive enzymes = poor digestion of food = increase osmotic potential of gut lumen
what are the 3 phases to cholera infection ? which phase can be/is fatal
- evacuation phase –> profuse watery ‘rice water’ diarrhoea and sometimes vomittin
- collapse phase –> caused by dehydration and decreased blood volume - can be fatal
- recovery phase - if you survive
why is it a selective advantage against cholera if you are a carrier of CFTR mutation gene
have half the number of CFTR channels so if you get cholera you lose less water - might survive
what would you check in a blood test for anemia in coeliac disease
components of erhypoeisis:
ferritin
folic acid
B12
what are the 3 components of the innate immune system
- toxic/ inhibitory substances
- complaint system
- cells which make up out in=immune system
give examples of toxic/inhibitory substances of the innate immune system
CRP- C reative protein (enhances phagocytosis)
deffensins in skin and gut
enzymes (lysozymes in tears)
what are the cellular components of the innate immune system
- phagocytes: neutrophils, monocytes, dendritic cells, eosinophils
- NK cells
- mast cells and eosinophils (release mediators- eg.histamine)
are T cells or B cells long lived
T cells are long lived most produced before puberty
B cells are short lived
where are B and T cells produced and matured
B cells are produced and matured in the bone marrow \
T cells are produced in the bone marrow and matured in the thymus
a region on which chromosome codes for MHC
region on chromosome 6
what are the antigens that MHC present called ? what is the significance of these antigens
Human leukocyte antigens : HLAs
HLAs are polymorphic and so its hard to find 2 individuals with matching HLAs so imunosupressents given in transplant
briefly describe humoral immunity
B cells trigged by matching antigen –> B cell engulfs and digests antigen —> displays antigen via MHC molecule –> attracts T-cell —> T cell releases cytokines —> helps B cell mature and multiply into plasma cells —> released into blood —> antigen antibody complexes formed —> removed via complement cascade
what are the 3 types of T helper cells ? describe their function
- Th1 –> promote inflammation, stimulator phagocytosis- responses to microbial pathogens
- Th2–> promote antibody production - specially IgE (involved in parasite and allergic reactions)
- Th17 –> roles in intestinal lamina propia
what are T helper cells also known as
CD4+ T lymphocytes
what are the 3 components of the mucosal immune system
GALT
intraepithelial lymphocytes
lamina propria lymphocytes
what are the components of GALT (gastric associated lymphocytic tissue)
- tonsils
- adenoids
- Peyers patches
- appendix
what are intraepithelial lymphocytes and where are they found
intersperse amongst epithelial tissues - contain mainly CD8+ T cells
what do lamina propia lymphocytes contain
CD4+ T cells, B lymphocytes, mast cells
what are the 3 IBD (inflammatory bowel diseases)
ulcerative colitus
Crohn’s disease
what is IBD
chronic relapsing and remitting inflammatory disorders of the intestines
what I the aeiotology if IBD
remains mainly unknown
what is the cure for IBD
no real medical cure
what is thought to be the trigger for the inflammorty response in IBD
inappropriate response to stimuli in genetically susceptible individuals
what are trigger stimuli in IBD
genes, environment, gut microbiome
where is Cronhs disease and where is ulcerative colitis located in the gut
Crohn’s –> anywhere in GI
ulcerative collitus –> colon/rectum
what is the disease distribution in crohns disease
full wall thickness
patchy ‘cobblestone’ appearance —> spaces with active inflation and normal intestinal cells in between
what is the disease distribution in ulcerative collitus disease
only effects the mucosa
continuous areas of inflammation
what are the histological findings in Crohns disease
- transmural inflamamtion (entire wall of intestine inflamed)
- granulomas –> spherical areas formed during chronic inflammation, if not degradable foreign matter or presence of pathogens present (absence of necrosis)
what are the histological findings in ulcerative collitus
mucosa and submucosal inflammation
crypt abcesses
gland destruction
lack of goblet cells
what are the complications associated with Crohns disease
- fistulas (abnormal connection between the GI tract and the outside to other organs in the abdominal cavity) - leads to perforation and abcess formation
what are the complications associated with ulcerative collitus
colonic dilation
toxic megacolon
which IBD does smoking improve disease course
ulcerative collitus
which IBD may surgery be a possible cure
ulcerative collitus as an remove part of colon or rectum
what are the symptoms of IBD
- diarrhoea
- rectal bleeding
- production of mucous in. stools
- faecal urgency
- incontinence (need to pee immediately)
- abdominal and perianal pain
- weight loss
- fatigue and lethargy
- mouth ulcers
what are mouth ulcers called
aphthous stomatitis
what are the signs of IBD
- abdominal tenderness
- mass on palpitation
- anaemia (caused by malabsorption )
- fistulae
- perianal abcess
what are dermatological extra intestinal manifestations of IBD?
erythema nodusum (painful fleshy bumps on skin) pyoderma gangrenosum (necrotic ulcer on legs) aphthous stomatitis (mouth ulcers)
what are musculoskeletal extra intestinal manifestations of IBD?
inflammation resulting in:
- peripheral arhtitius
- sacroileitis (inflation of sacroiliac joint)
- ankylosing spondylitis (arthritis in spine)
- osteoporosis
what are vascular extra intestinal manifestations of IBD?
vasculitis
venous thromboembolism
what are ocular (eyes) extra intestinal manifestations of IBD?
- aveitis
- iritis
- scleritis
what are renal extra intestinal manifestations of IBD?
- kidney stones
- glomeruloneptitis : inflation of glomeri
- tubulo-intestinal nephritis : inflammation of intestinal tissue surrounding tubules of kidney
what are hepatobillary extra intestinal manifestations of IBD?
primary sclerosing cholargitis
what is the first line of treatment we would use for Crohns disease
short term anti-inflammatory : corticosteroids
to induce remission
what is the second line of treatment we would use for Crohns disease to maintain remission
- immunosuppressants : azathioprine, 6-mecraptoparine
- aminosaclicylates : for disease in the colon (mesalazine)
- methotrexate: anti inflammatory and immunosuppressant
- antibiotics
how do aminosalicylates work
aspirin analogues are broken down in the colon providing aspirin directly to the colon
how does azathioprine works as an immunosuppressant
converted to 6-mercaptopurine —> purine analogue incorporated in DNA –> = poor proliferation of leukocytes = suppression of immune system
what is infliximab
a biological therapy of monoclonal antibodies against TNF-a
what does infliximab contain
human constant region and mouse variable region = chimeric
what does chimeric mean
consisting of material from 2 differnt species
how does infliximab work
binds to TNF-a on surface of T cells –> indices apoptosis of inflammatory cells and reduced amount of TNF
name 5 autoimmune diseases other than IBD
diabetes 1 (organ specific) graves (organ specific) MS rheumatoid arhtitis systemic lupus erythematous coeliac disease myasthenia gravis
which sex do autoimmune diseases mainly effect
females
what are the diagnostic features of anorexia nervosa?
active maintenance of low body weight (<85% of expected weight or BMI <17)
extreme shape and weight concern
give some physical signs of anorexia nervosa?
sever weight loss low blood pressure constipation and bloating hair falls out and downy hair over body swelling in feet and hands low body temperature periods stop
what was the minnesota experiment?
study of human starvation with 36 conscientious objectors in WWII
3 month stability phase on 3600 kcal followed by 6 month starvation phase on 1800 kcal
what are the diagnostic features of bulimia nervosa?
recurrent binge eating
compensatory behaviour (vommiting, laxatives, fasting, exercise)
extreme shape and weight concern
binge 1/week for 3 months
what are physical signs of bulimia?
fatigue stomach pain and constipation regular changes in weight enlarged salivary glands electrolyte imbalance swelling of hands and feet
what is the difference between binge eating disorder and bulimia nervosa?
binge eating disorder has no compensatory behaviour
what do eating disorders have in common?
behaviour around food (restriction)
core beliefs and associated concerns
levels of distress (mood disorders?)
what might make someone more likely to develop an eating disorder?
mental health problems family history perfectionism history of dieting being part of a sport or activity with emphasis on appearance
what are the specific risks for eating disorders?
body dissatisfaction (contextual, physical and developmental)
- negative body image
- weight preoccupation
- dietting
what are non-specific risks for eating disorders?
self-regulatory (parental physcopathology, trauma, biological predispositions)
- low self esteem
- affective dysregulation
- insecure attachment
what are the three stages of ed treatment?
weight management
psychological therapies
relapse prevention
what is the most common mutation of CFTR
F508del
what are the symptoms of CF
- airways clogged with mucous
- chest infections
- persistent cough
- pancreatic insufficiency
- CF related diabetes
what does cross infection refer to in CF
CFs cant mix as bugs in lungs are transmissible between patients and dangerous
what is the medication used in CF
- 50 different pills a day: inc pancreatic enzymes
- physiotherapy
- nebulisers
- inhalers
- insulin
- supplement drinks
why do people with CF have a high fat diet
- pancreatic insufficiency
- stable BMI helps fight infections
- helps regain weight
- malabsorption of vitamins and minerals
- strong correlation between weight and lung function
what is percutaneous endoscopic gastrostomy in CF
used for weight management = instant liquid feed fitted directly into stomach to help patients regain weight
CF in diabetes can lead to a problem with the use of ….
steroids
what are other related complications with CF
- osteoporosis
- liver disease
- kidney disease
- CF related arthritis
- sinus issues (polyps)
- infertility in males
- bowel cancer
how many years can a transplant extend a CFers life
5 years
