MET1 Flashcards
What is oral lactulose used to treat? [1]
Constipation
Explain what a Fibroscan measures and how this occurs [2]
Non invasive procedure to assess the health of the liver.
Probe is placed on the surface of the skin. Elastic wave & ultrasound: get a measure of stiffness of the liver – indicates scarring / fibrosis: leads to cirrhosis and liver cancer
What type of imaging is a fibroscan? [1]
Ultrasound
When is ALT released? [1]
ALT released when liver cells lyse – higher in liver failure than other types. ALT is released in other organs, so the ratio can be used to determine liver failure
What is pabrinex and explain which pathology it may prevent by providing it [2]
Pabrinex: provides additional vitamins B and C to correct deficiencies that may have occurred. Incudes Thiamine. Thiamine deficiency can lead to Wernicke Encephalopathy
Desribe the action (and site of action) of terlipressin
- Terlipressin: is a synthetic analogue of vasopressin, which is an endogenous neurohormone that acts as a vasoconstrictor – maintains pressure for the kidneys
When is terlipressin indicated? [1]
oesophageal varices.
How do you treat Hepatic Encephalopathy? [1]
Lactulose: clears toxins from your blood by leading to frequent bowel movements, with less time for ammonia absorption and increased fecal nitrogen excretion.
When perfoming an ascites tap, what structure do you need to avoid?
- Ascites tap: performed in the right or left lower quadrant of the abdomen. Need to avoid inferior epigastric artery which runs within the rectus sheath approximately 4-8cm from the midline. Drain the abdomen of fluid
INR testing measures the function of which clotting factors? [4]
What is normal INR? [1]
Does high or low INR cause longer blood clotting time? [1]
- INR testing: The INR measures the function of a limited number of clotting factors (fibrinogen, II, VII, IX, X).
Normal INR is 1.0
The higher your PT or INR, the longer your blood takes to clot
What are the main main effector cells of liver fibrosis? [1]
stellate cells
Explain the difference between compensated and decompensated cirrhosis
Compensated cirrhosis:
1. Liver function is preserved
2. May be asymptomatic but still have increased risk of e.g liver cancer
3. no evidence of complications related to portal hypertension, such as ascites, gastro-oesophageal varices and variceal bleeding, hepatic encephalopathy, and/or jaundice
Decompensated cirrhosis
1. Complications of liver dysfunction: umbrella term for a spectrum of disease
2. reduced hepatic synthetic function and portal hypertension including ascites, gastrooesophageal varices and variceal bleeding, hepatic encephalopathy, and/or jaundice.
Describe the pathophysiology of cirrhosis [3]
State 4 disease it can lead to [4]
Hepatic fibrosis leads to cirrhosis with nodule formation. Prevents regeneration
* Activation of hepatic stellate cells: cause accumulation of collagen type I and III in the hepatic parenchyma and space of Disse
* Stellate cells also become more contractile
* Accumulation of collagen causes altered exchange between hepatocytes and plasma
* Disrupts blood flow and causes increased pressure in the portal venous system: portal hypertension, causing:
i. Ascites
ii. Gastro-oesophageal varices
iii. Rectal varices
iv. Promotes the diversion of nutrient carrying blood away from the liver and cause hepatic encephalopathy
Explain the results
Low Hb, Low plts and High INR: liver disease causes coagulation disorder leading to bleeding and subsequent anaemia.
Low albumin: the liver makes less albumin leading to deviations of the equilibrium between osmotic pressure and hydrostatic pressure in the blood vessels. Low albumin along with portal hypertension, results in the patient suffering from ascites and oedema. Albumin is also a marker of nutritional status.
High bilirubin: bilirubin (waste product from the breakdown of RBC). The liver has reduced ability to conjugate bilirubin, so it can’t be excreted, leading to high levels being present in blood. This causes jaundice
.
High ALP, AST, ALT and GGT: these liver enzymes are present at higher levels in the blood when leaking out of dying hepatocytes. Not extremely as liver was previously damaged by HCV.
High urea: main nitrogenous breakdown product of protein metabolism. High urea due GI bleeding being digested as a “protein rich meal”.
Low end of normal glucose: liver is unable to maintain blood glucose level due to damage.
Why are elevated levels of ALT & AST used to detect liver disease? [2]
Aminotransferases are enzymes contained in hepatocytes and leak into the blood with liver cell damage. Two enzymes are measured:
Aspartate aminotransferase (AST) is primarily a mitochondrial enzyme (80%; 20% in cytoplasm) and is also present in heart, muscle, kidney and brain. High levels are seen in hepatic necrosis, MI, muscle injury and congestive cardiac failure.
Alanine aminotransferase (ALT) is a cytosolic enzyme, more specific to the liver, so that a rise only occurs with liver disease, when liver cells lyse and release this into the blood.
Alkaline phosphatase (ALP) is present in hepatic canalicular and sinusoidal membranes, and also in bone, intestine and placenta.
What else other marker being abnormal indictes that ALP is from the liver? [1]
In clinical practice, if the γ-GT is also abnormal, the ALP is presumed to come from the liver
Diagnosis of cirrhosis?
Diagnostic paracentesis in new-onset ascites
1. Aspiration of ascitic fluid and its laboratory analysis is an essential step in the management of patients with newly diagnosed ascites.
2. Fluid is analysed for protein and white cell count. Protein count can help differentiate whether the cause of ascites is cirrhosis or whether the ascites is due to other causes like heart disease or cancer
Transient elastography / fibroscan
1. measuring liver stiffness, which is correlated to the histologic stage of liver fibrosis. Normal liver stiffness ranges between 3.3-7.8 KPa
(& liver function tests)
Explain the consequences of liver failure on the metabolic state [2]
Which energy store is the patient with decompensated liver most likely using as main energy supply? [1]
(There are similarities to the starved state here)
- Blood glucose is on the low side and this is symptomatic of the liver not being able to store glycogen/do glycogenolysis and gluconeogenesis thus blood glucose homeostasis will be impaired.
- Similarly, ketones are unlikely to be as high as they would if the liver was fully functioning. In this case, the patient is likely to be using fats as their main energy supply.
Explain why gallstones made lead to a prolonged INR? [1]
Lack of bile salts gives malabsorption of fats and slows absorption of fat-soluble vitamin K, which is required for synthesis of some clotting factors including prothrombin.
A portal pressure above [] mmHg causes portal hypertension? [1]
Pressure rise above 14 mmHg (usual: 5-10 mmHg)
Explain why hepatic encephalopathy is a complication of liver cirrhosis [3]
Ammonia: the liver clears almost all of the portal vein ammonia, converting it into glutamine and urea, preventing entry into the systemic circulation. Ammonia is a by-product of the metabolism of nitrogen-containing compounds, and is neurotoxic at elevated concentrations.
GI bleeding: the presence of blood in the upper GI tract results in increased ammonia and nitrogen absorption from the gut.
Aromatic amino acids (AAA): the increase in plasma AAA, resulting from a change in the** ability of the liver to process them** has been suggested to contribute to an increased influx in the brain leading to imbalances in neurotransmitter synthesis.
Explain why spontaneous bacterial peritonitis is a complication of liver cirrhosis [2]
Weakened immune system
- The liver contains 90% of the reticuloendothelial (RE) cells, such as Kupffer and sinusoidal endothelial cells, which are central to clearing bacteria.
- Most of the proteins of the “complement system” (part of the immune system that enhances the ability to clear microbes) are made by the liver. This increases the risk of bacterial peritonitis and thus the need for antibiotics
[] is an indicator of kidney function.
Creatinine is an indicator of kidney function.
1)A fibroscan is a very useful technique to assess liver damage from conditions such as Hepatitis C. (i) What tissue property does a fibroscan measure in the liver? [1 mark]
Level of fibrosis / scarring of the tissue due to increased type 1 and 3 collagen. Unit is kPa
2) (i) What type of information does the AST:ALT ratio give? (ii) What ratio is suggestive of alcoholic liver disease? [2 marks]
(i) This enables the differentiation of liver disease from other diseases and can also suggest the potential cause of the liver disease. Alcohol or NAFLD 1 mark]
(ii) A ratio of 2:1 [1 mark]
3) (i) What role does the liver plays in immunity? (ii) Why is the patient at risk of infection? [2 marks]
Weakened immune system due to reduction in energy metabolism, reduced formation of complement system protein, compromised reticuloendothelial function (Kupffer cells etc…) [1 mark].
Build-up of fluid increases risk of infection (providing a perfect 37C niche for bacterial growth) [1 mark]
5) Pabrinex, Lactulose and terlipressin are all part of the treatments for decompensated liver cirrhosis: describe their mode of action. [3 marks]
Pabrinex
* (via intravenous injection) provides these: mix of B vitamin (essential for a range of bodily processes and form part of the co-enzyme involved in carbohydrate, protein and lipid metabolism). (i) Thiamine is an important co-factor for the conversion of Pyruvate to AcetylCoA (which feeds into the Krebs cycle). If Thiamine is lacking, then Pyruvate forms lactic acid instead (which is neurotoxic).
Pabrinex also contain glucose, as the liver has impaired gluconeogenesis. [1 mark]
Lactulose - By acidifying the contents of the gut, lactulose reduces the absorption of ammonia from the gut, thereby helping to prevent encephalopathy. [1 mark]
Terlipressin - (analogue of vasopressin). It is important to reinstall correct blood circulation and support kidney function. (Main factors in the pathophysiology of hepatorenal syndrome are splanchnic vasodilation and increased cardiac output).
[1mark]
What type of viruses are Hep A-E [1]
Hep A: RNA virus
Hep B: DNA virus
Hep C: RNA virus
Hep D: RNA virus
Hep E: RNA virus
Describe mode of transmission for Hep A [1] and Hep B viruses? [1]
Hep A: faecal-oral route (contanimated water)
Hep B: Blood bourne / vertical transmission
What pathology does Hep A cause? [1]
cholestasis
State two complications of Hep C infection [2]
liver cirrhosis and associated complications and hepatocellular carcinoma
Hepatitis D can only survive in patients who also have which of the follwowing hepatitis infections:
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis E
Hepatitis B
What are normal kPa fibroscan scores? [1]
2-7kPa is normal, highest is 75
The four most common causes of liver cirrhosis are? [4].
- Alcoholic liver disease
- Non Alcoholic Fatty Liver Disease
- Hepatitis B
- Hepatitis C
What is a tumour marker for hepatocellular carnicoma? [1]
Alpha-fetoprotein is a tumour marker for hepatocellular carcinoma and can be checked every 6 months as a screening test in patients with
cirrhosis along with ultrasound.
Describe appearance of arteries of cirrhotic liver [1]
- A “corkscrew” appearance to the arteries with increased flow as they compensate for reduced portal flow
Describe how cirrhosis leads to malnutrition and muscle wasting [2]
increased use of muscle tissue as fuel
and reduces the protein available in the body for muscle growth.
It also disrupts the livers ability to store glucose as glycogen and release it when required.
Most common organisms or Spontaneous Bacterial Peritonitis (SBP) due to ascites? [3]
Management of SBP? [2]
Organisms
* Escherichia coli
* Klebsiella pnuemoniae
* Gram positive cocci (such as staphylococcus and enterococcus)
Management of SBP:
* Take an ascitic culture prior to giving antibiotics
* Usually treated with an IV cephalosporin such as cefotaxime
Which drug reduces the number of intestinal bacteria producing ammonia? [1]
rifaximin
