MET2 Revision 9 Flashcards
How does liver disease progress? (is similar for no. of pathologies)
- Primary Injury: liver cells are damaged.
2.This causes inflammation
- This causes liver cell injury / death from primary injury or inflam. response
- Fibrosis occurs if cell death is too advanced / regen capacity is exhausted / process has been to extensive: causes pathological scar tissue (fibrosis).
- Eventually fibrotic nodules are formed: this is when we classify as cirrhosis
- A liver can function normally with cirrhosis (& be asymptomatic) but can lead to liver failure or cancer
Symptoms of liver disease?
Systemic [2]
Cholestatic? [2]
None
Systemic:
* Weight loss
* Tiredness
Cholestatic (reduction in bile flow)
* Pruritis (itchy skin; Cholestatic liver disease increases levels of bile salt which accumulate under the skin causing itch)
* Pale stools/dark urine
Complications of underlying disease
Signs of Chronic Liver Disease? [5]
Palmar erythema
Spider naevi
(most specific)
Hair loss
Gynaecomastia (man boobs)
Leuchonychia / Clubbing
Proximal wasting
Scratch marks
Xanthelasma
Indicators of liver status:
Which blood tests would be useful to indicate liver function? [2]
Which blood tests would be useful to indicate stage of liver disease? [2]
Which blood tests would be useful to indicate liver function? [2]
* Albumin
* INR (Prothrombin Time)
Which blood tests would be useful to indicate stage of liver disease? [2]
* Platelet count (as spleen enlarges, can have consumption of platelets)
* ALT/AST
What would be indicated if ALT / AST is raised? [1]
Elevated ALT / AST indicates source is hepatic problem
What would be indicated if Alk Phos AND γGT/ GGT is raised? [1]
Elevated Alk Phos / γGT indicates cholestatic problem
What could be ruled out of causing ALT > 500?
What would ALT of 500-100 indicate is the source?
What would ALT of 1500+ indicate?
ALT:
Alcohol doesn’t put ALT > 500
500 – 1500: autoimmune hepatitis
more than 1500: hepatitis viruses / drugs / ischaemia
Which results in blood tests would help ID aetiology? [3]
Aetiology:
Viral markers
Autoantibodies & Immunoglobulins
Metabolic
* Ferritin / caeruloplasmin / HbA1c
* Alpha1 antitrypsin
* Alphafetoprotein
First Imaging used for liver disease? [1]
What are alternatives? [4]
Ultrasound:
* Biliary tree
* Liver lesions
* Ascites
* Spleen
* Veins
* Other pathology
CT
MRI
ERCP / MRCP
How does cirrhosis cause portal hypertension?
Name 3 signs of portal hypertension [3]
- Cirrhosis disrupts the blood flow into the flow from the portal veins: causes increase in pressure (portal hypertension)
- Liver breaks down vasodilatory peptides (if not working, then doesn’t)
- If liver is also not producing albumin, decreases oncotic pressure and pushes liquid out
Dilated abdominal veins
- Caput medusa
Ascites
Splenomegaly
Explain how portal hypertension causes ascites
Liver malfunction:
* Liver breaks down vasodilatory peptides (if not working, then doesn’t)
* Cirrhosis reduces ease of blood flow
* If liver is also not producing albumin, decreases oncotic pressure and pushes liquid out
Causes splachnic vasodilation
Causes reduction in circulating volume in portal system.
(sensed by the kidney (by JGA))
Activates renin system: causes activation of RAAS. Leads to salt and water reab. at kidney
Leads to ASCITES
How can you treat variceal bleeding [4]
What can you give as primary and secondary prophylaxis for variceal bleeding? [2]
Treatment:
Resuscitation
Terlipressin (inhibits portal hypertension with simultaneous reduction of blood circulation in portal vessels) and Antibiotics
Banding or injection sclerotherapy
TIPSS
Primary + secondary prophylaxis beta blockers
Propranolol / Carvedilol
Banding
How is ammonia produced in health? What happens after this?
NH3 is produced when glutamine converted to glutamate
In health: NH3 is converted to urea & excreted in kidney OR in reverse of reaction, back to glutamine
How can you stop the production of NH3 to treat encephalopathy? [2]
Rifaximin: reduces the production of NH3 in the gut
L-Ornithine L-arginine: stops the conversion of glutamate to glutamine
What scoring system do you use to assess if have decompensated liver? [1]
What score would classify a decompensated liver? [1]
Child-Pugh score:
over 7 points: decompensated
What is non-alcholic fatty liver disease? [2]
Hepatic steatosis build-up of fat in the liver cells) on histology or imaging
No secondary cause for steatosis
Explain how insulin resistance causes a higher risk of developing fatty liver disease [3]
Insulin Resistance causes high risk of developing fatty liver disease.
Patient resistant: have high levels of circulating glucose: causes de novo lipogenesis in liver cells
Also causes inappropriate gluconeogenesis, impaired glycogen synthesis AND decreases the suppression of lipids in the liver
Overall: causes more glycerol, long chain fatty acids that make way to liver and hepatic fats accumulate. Also get impaired clearance of via VLDL formation
Which three process due to fat accumulating in the liver causes the progression to fatty liver disease? [3]
Oxidative Stress (lioptoxicity)
Inflammation
Innate immune activation
Which pathology is commonly associated with ALD? [1]
What does this pose a risk or when re-feeding? [2]
Nutritional deficiency
* Poor oral intake and ‘empty calories’
* Possible re-feeding risk
* Thiamine and vitamin deficiencies
Which diseases can occur if you do not have enough Thiamine? [2]
Replace thiamine early
* Wericke’s encephalopathy
* Korsakoff’s syndrome
What effect does low pH on the body if it is out of control acutely? [4]
Acutely:
* Negatively inotropic
* ‘Air hunger’: panting away
* Part of critical illness syndrome – generalised cellular dysfunction
* Affects body K+ distribution (net shift of K+ from the intracellular to the extracellular space)
What happens when low pH is out of control chronically? [3]
- Effect of bones and stone formation
- Associated with progression of kidney disease
- Paradoxical relationship with mortality
Name 3 ways that acid is constantly being added to body [3]
- Cellular respiration: after Co2 & H20 produced - get CA converting to HCO3- & H+. Roughly 15mol/d
- Dietary acid (titrable): amino acids from diet protein. Roughly 60mmol/d of sulphuric and phosphoric acid from diet
- 3) Other physiological and pathological states – eg exercise (lactic acid), ketoacidosis (uncontrolled diabetes - use ketones instead of glucose as fuel source, which are acidid)
Why would sepsis cause acidosis?
In sepsis: constrict small arterioles of limbs, gut and skin: they’re all metabolizing anaerobically: lactic acid
What is Henderson-Hasselbach equation in the body for pH blood plasma? [1]
How does infusing a Ptx with acid effect the Ptx? [1]
Causes decrease of serum bicarbonate. Drives equation to left: causes increase in PCO2: blow off the acid as CO2 because now hyperventilation
Mechanism of reabsorbing HCO3- at PCT ?
Excrete acid in urine
Regenerate HCO3- at DCT & CD?
What is the name of the cells where this occurs?
What are the two main urinary buffers? [2]
In alpha intercalated cells:
- the α-intercalated cell (IC) of the collecting duct (CD) is critical for renal acid secretion and helps maintain acid-base balance.
- pushes out protons into urine. BUT can only does this for certain amount.
- Need urinary buffers to be excreted to soak up the protons, so can keep excreting them.
Two main urinary buffers:
- Titrable acid (NaH2PO4)
- Ammonium system – can generate more buffer. NH3 NH4+
Hyperventilation causes acid / alkolosis?
Hypoventilation causes acid / alkolosis?
Hyperventilation causes alkolosis: expelling more CO2
Hypoventilation causes acidosis
How can you cause metabolic acodosis? [4]
Adding Acid to your body:
- Ingestion of acid (Aspirin)
- Generation of acid (lactic acid, ketones)
- Retention of acid (renal failure)
Loss of bicarbonate:
- Gut – eg diarrhoea, Kidneys - RTA
What is hyperchloremic metabolic acidosis?
What is the most common cause? [1]
More rare cause? [1]
Normal anion gap acidosis is an acidosis that is not accompanied by an abnormally increased anion gap.
Caused by loss of HCO3- WITH a compensatory rise in Chlorine
Most common cause: diarrhoea
Also caused by: renal tubular acidosis
What is high anion gap acidosis?
Caused by? [4]
Addition of exogenous acid: NO COMPENSATORY RISE IN Cl-
Commonest causes:
* Lactic acidosis
* Ketoacidosis
* Renal failure
* Poisoning
What is metabolic alkalosis caused by? [overview]
Occurs mostly due loss of chloride: so get HCO3- rise:
- Chloride (HCl) – in vomiting/NG aspiration
- Chloride – through diuretic use
- Potassium – through the effect of aldosterone
- Ingestion of alkali
*
What is metabolic alkalosis caused by? [4]
Occurs mostly due loss of chloride: so get HCO3- rise:
- Chloride (HCl) – in vomiting/NG aspiration
- Chloride – through diuretic use
- Potassium – through the effect of aldosterone
- Ingestion of alkali
*
What is Normal anion gap acidosis aka? [1]
= hyperchloremic metabolic acidosis
What can cause hyperventilation? [3]
(and therefore resp. alkalosis)
- Any cause of impaired oxygenation !! Important (This is because these people frequently breathe faster than normal when trying to get more oxygen into the body)
- Central cerebral stimulation: fever, pain, drugs, sepsis
- Panic/anxiety
What can cause resp. acidaemia? [3]
Reduced ventilation:
* Airways disease: COPD
* Neuromuscular or chest wall disease
* Reduced respiratory drive: opiates or reduced consciousness
What are o2 sat. targets for COPD Ptx? [1]
88-92
What are the characteristics of compensated resp acidosis:
pH? [1]
pCO2? [1]
HCO3-? [1]
- Normal pH
- high pCO2
- compensatory high HCO3-
Why would someone commonly present with metabolic acidosis with partial resp. compensation? [1]
Diabetic patient: have DKA - causes ketoacidosis
What could cause high anion gap metabolic acidosis? [4]
Acid ‘added’ to the blood:
Ketones:
* DKA
* Starvation or alcoholic ketoacidosis
Lactate:
* Tissue hypoxia/poor perfusion
* Altered cellular respiration
* Rarely: D-lactate
‘Titrable acid’
* Renal failure
Ingested acid
* Ethylene glycol, methanol, salicylate…
How does lactic acidosis / ketoacidosis commonly present with regards to:
- pH
- HCO3-
- CO2
Low pH, low HCO3-, often low CO2
What does lactic acidosis / ketoacidosis commonly present as? [3]
Low pH, low HCO3-, often low CO2
What happens to serum K+ levels in severe acidosis?
Go up (as exchange of H+ causes to go otherway)
What are normal anion gap, metabolic acidosis characterised by? [1]
Increased Chlorine levels / = ‘Hyperchloraemic metabolic acidosis’
Compensatory rise in chloride to maintain electrical neutrality
Hes losing bicarbonate
What would cause normal anion gap metabolic acidosis?
= ‘Hyperchloraemic metabolic acidosis’
Usually due to bicarbonate loss
* Kidneys: Renal tubular acidosis
* Gut: diarrhoea
Compensatory rise in chloride to maintain electrical neutrality
Why might HCO3- rise in Ptxs? [4]
As H+ is lost:
* Diarrhoea
* Diuretics
* Mineralocorticoid excess
* Vomiting/NG drainage
As H+ moves into cells: Hypokalaemia
The best liver function test is:
a. AST/ALT
b. Alkaline phosphatase
c. Bilirubin
d. INR
The best liver function test is:
a. AST/ALT
b. Alkaline phosphatase
c. Bilirubin
d. INR
Of the above, only the INR is a true liver function test as it examines the capacity of the liver to synthesize clotting factors. AST and ALT are enzymes that are elevated in hepatocellular injury. Alkaline phosphatase is an enzyme that is elevated in cholestatic injury. Bilirubin is a pigment secreted by the liver that is elevated with liver dysfunction but can also be elevated with bile obstruction (even though liver function is normal).
The following statements are all true, except:
a. Hepatic stellate cells produce bile
b. Bile formed in the liver is transported to the gut
c. Bile helps digest fat
d. Cholesterol forms a part of bile
The following statements are all true, except:
a. Hepatic stellate cells produce bile
b. Bile formed in the liver is transported to the gut
c. Bile helps digest fat
d. Cholesterol forms a part of bile
