Unit 10: Alcohol related liver disease and domestic abuse Flashcards
What is the impact of stress on GI function?
Stress diahorrea - increased motility in the distal git, reduced transit time and increased stool output, defense to eliminate toxins
Later - likely to experience constipation, as reduces GIT motility in the upper GIT, thought to be a protective mechanism to decreases oral intake and promote vomiting to remove any toxins
These responses are mediatores yb CRF. CRF 1 receptors stimulates in the colon and CRF2 receptors decrease upper GIT activity.
Change to gut microflora - increases risk of opportunistic infections
Instential sensitivity increases with stress - increase heartburn or pain sensations.
What are the physiological reasons to feel run down?
Insomnia/sleep problems - cause acute fatigue or sleep debt,
Hypothyroidism - reduced BSM, reduced energy production
Alcohol or drug intake - disrupted sleep - often fragmented and early waking due to elevated adrenaline a few hours after consumption, decreased ADH wake up to urinate.
Central fatigue - CNS decreased stimulation of motor neurons, reduced motor initiation
Peripheral fatigue - reduced calcium ion conc, depleted muscle ATP supply.
What are the psychological effects of feeling run down? **
Increased risk of mental health conditions such as anxiety and depression.
What is the cause of jaundice in liver failure?
Damaged hepatocytes can no longer conjugate bilirubin or secrete bilirubin into bile.
Accumulation of (un)conjugated bilirubin in the plasma.
Decreased albumin (unable to transport unconjugated bilirubin to the liver)
Has a yellowish pigmentation causing jaundice appearance when present in high concentrations.
What is the cause of oedema in liver disease?
Cirrhosis of the liver increases resistance to blood flow.
This causes portal hypertension.
Causes blood pooling in the portal vein and associated tributaries.
This increases the hydrostatic pressure of these vessels and decreases the relative oncotic pressure - results in net movement of fluid out of the vessels and into the ECF.
This can be worsened as reduced venous return to the heart can trigger baroreceptors to activate sympathetic tone resulting in RAAS activation in the kidneys exaggerating fluid accumulation by reducing fluid and salt loss int he urine
What is the pathology behind alcoholic liver disease?
Accumulation of acetaldehyde (toxin) damages hepatocytes and dysregulates metabolism
Alcohol metabolism results in an accumulation of NADH and reduced NAD+.
A low NAD+:NADH ratio favours lipogenesis over beta-oxidation (lipolysis), which results in fat accumulation within hepatocytes.
Damaged hepatocytes produce less lipoprotein so less binding to and transporting of fat (cholesterol out of the liver)
Describe the effect of fatty liver disease on carbohydrate metabolism?
Ethanol metabolism results in decreased NAD+: NADH ratio results in decreases glycolysis and gluconeogenesis, results in an increase in anaerobic respiration.
Results in an accumulation of lactic acid, resulting in lactic acidosis.
What are the histological changes associated with Fatty liver disease?
Fat droplet accumulation of varying size.
Large droplets puch nucleus to the periphery
Fat accumulation normally starts as the central vein and spreads outwards into zone 2 and 1 of hepatocytes
May have some fibrosis in a chicken wire fashion around the central vein
What is the underlying mechanism of alcoholic hepatitis?
Acetaldehyde is a toxin produced in alcohol metabolism, causes lipid peroxidation of the cell membranes, impairs the membrane function and forms DNA/protein adducts. Damaged hepatocytes acts as DAMPs to trigger inflammation.
Accumulation of ROS causes oxidative stress in the liver.
Can exaggerate damage and further trigger inflammation - leading to neutrophil infiltrates.
What are the histological changes in alcoholic hepatitis?
Hepatocyte ballooning - swellling can indicate early signs of necrosis
Mallory Hyaline bodies - tangled intermediate filaments such as keratine seen as eosinophilic inclusions
Neutrophil/immune infiltrate.
What is the pathology of alcoholic liver cirrhosis?
Liver injury occurs damaged hepatocytes secrete DAMPs and ROS.
Activated kupfer cells secrete pro-inflammatory cytokines such as TNFalpha, this activates stellate cells in the space of Disse.
Triggers stellate cells to become myo-fibroblast like meaning they secrete and deposit collagen in the space of Dissee, this reduces the space and results in fibrosis.
Also secrete chemokines such as CCL2 to attract more immune cells.
TGF beta leads to more collagen deposition and exaggerates fibrosis of the liver.
Eventually, functional liver architecture is replaced by fibrosis (nonfunctional) results in cirrhosis.
Often creates regnerative nodules
What are the histological changes in liver cirrhosis?
Is often diagnosed histologically with fibrosis first occurring around the portal triads, then branching out to connect the different portal triads by periosinusoidal scarring in the space of Dissee, severe bridging forms fibrous septa between areas of hepatocytes, which are no longer in the uniform hexagonal arrangement around the central vein, these new abnormal architecture clusters are called hepatic regenerative nodules and are a key features of cirrhosis.
Fibrous tissue around irregular hepatocyte aggregates
What are the gross changes in alcoholic liver disease?
Looses red and smooth appearance
Becomes more yellow and large in appearance, original with accumulation of fat on the surface
As progresses to cirrhosis gain regenerative nodules on the surface and inside.
Hepatomegaly is common.
In severe late stage, the liver often shrinks in size as fibrosis replaces the functional liver architecture.
What are the effects of alcohol withdrawl?
Tolerance develops to alcohol - neurological changes, decreased GABA receptors and increased glutamate receptors means the brain is in a hyperexcitable state when the CNS depressant effects of alcohol are removed.
Neural membrane is more likely to be depolarised resulting in an increased frequency of action potentials.
This can result in seizures, tremors, anxiety, agitation, tachycardia, hypertension and delirium.
How is alcohol withdrawal syndrome managed?
Clinical Institute Withdrawl Assessment for Alcohol - tools used to score patients on their withdrawal symptoms and indicate the level of intervention required, combined 8 or higher score meaning intervention needed.
Medicate with benzodiazepines (CNS depressant, allosteric effect at GABA A receptors) resulting in hyperpolarised neurone - gradually reduce dose
High dose vitamin Bs - often IV or IM - followed by long term oral thiamine to prevent Wernicks-Korsakoff syndrome
What is the cause of bruising in alcoholic liver disease?
Due to decreases platelets (below 140x10^9).
Liver is the site of thrombopoietin production, which acts on bone marrow to encourage magakaryocytes to become platelets through cytoplasmic budding.
Liver damaged - means decreases thrombopoietin - leads to reduced platelet production
What is the cause of ascites in alcohol related liver disease?
Cirrhosis = portal hypertension.
Blood pooling in the splanchnic arterioles - increased hydrostatic pressure and reduces relative oncotic pressure (worsened by decreased albumin) causes fluid leakage into peritoneal cavity.
Reduced venous return to the heart, triggers sympathetic nervous system efferents, alongside baroreceptor activation in the carotid sinus.
Leads to efferents to increase blood volume and blood pressure - activate RAAS system and vasoconstriction in portal system.
Pooling causes NOx released into splanchnic arterioles increase blood trying to flow into liver - increases portal hypertension and exaggerates ascites.
What is the cause of splenomegaly in alcoholic liver disease?**
Portal hypertension - causes blood pooling along the splenic vein which drains into the portal vein, accumulation of blood causes the spleen to grow in size.
What is the cause of oesophageal varices in alcohol related liver disease?
Portal hypertension - blood tries to find a route of less resistance, results in blood pooling
Increased volume of blood in the portosystemic anastomosis areas - results in varicocele veins.
This can be seen in the oesophagus, in the rectum (cause rectal bleeding) and as caput medusa if the round ligament is recanalised.
What is the mechanism of action of spironolactone?
Potassium sparing diuretic
Is an aldosterone receptor antagonist.
Competiitivly binds to aldosterone receptors at the DCT and the CD.
This inhibits the increase in ENaC channels and Na+/K+ pump.
Results in decreased Na+ reabsorption, increases the osmolarity of filtrate, reduces water reabsoprtion resulting in a larger volume of more dilute urine.
Why is spironolactone taken in alcoholic liver disease?
Is a potassium sparing diuretic.
Helps encourage fluid loss in the urine - this helps decrease ascites.
Why is lactulose taken in alcoholic liver disease?
Small effect on ascites - by reducing fluid levels in the body (laxative).
(Metabolised to acidic components) Main effect is to counteract levels of ammonia (neurotoxin) prevent the development of Wernicks encelopathy
What is the mechanism of action of lactulose?
Synthetic disaccharid derivative of lactose
Laxative
Broken down in the large intestine by colonic bacteria into acetic acid, lactic acid and formic acid.
Increases osmotic pressure to draw water into lumen
Distends intestine increasing peristalsis
Acid lowers pH, which increases mineral absorption into colon and prevents NH3 absorption into the blood stream,
Acidic environment converts NH3 into NH4+, excreted reducing plasma ammonia concentration.
Why are intravenous vitamins needed in alcoholic liver disease treatment?
Alcohol impairs the absoprtion of vitamin
Also alcoholics tend to replace food with alcohol - so they also have reduced intake
This can cause anaemias, malnutrition and even contribute to cognitive difficulties such as wernickes encelopathy.
What vitamins are alcoholic normally deficient in?
Vitamin B1 (thiamine)
Vitamin B6
Vitamin B9
Vitamin A,C,D,R,K and B are often affected aswell
What is the role of vitamins that are deficient in alcoholic liver disease?
Vitamin B1 thiamine - helps turn food into energy and keep the nervous system healthy
Vitamin B6 - helps function sugars, fats and protein. Development of brain, nerves, skin etc
Vitamin B9 (folate) ; red blood cell formation and healthy cell growth and function
What vitamin solution is often given to alcoholics?
IV pabrinex - includes thiamine alongside other B vitamins and C vitamins
If before surgery may also be given vitamin K, as this is important in coagulation factor production and thickening blood - reduce the risk of bleeding out. (damaged liver produce less coagulation factors)
What blood tests might the doctor order to diagnose IBS?
Negative for Inflammation markers - CRP
Normal white blood cell count
Negative for autoantibodies antibodies tTG for coeliac disease
Negative hydrogen breath test to rule out lactose intolerance.
