Cirrhosis Flashcards
Name and explain the 4 stages of liver disease
Hepatic steatosis: accumulation of triglycerides in the liver - disrupts the function
Fibrosis of the liver: continuous damage and repair will form fibrous tissue. Still functioning, but preventative measures needed
Liver cirrhosis: excessive scarring, fibrous tissue replaces healthy liver tissue. Permanent and liver becomes hard and lumpy
Liver failure: end stage of liver disease and is complete loss of function
What are the stages of liver cirrhosis? include symptoms
Compensated: asymptomatic, liver can perform vital functions
Decompensated: fibrous tissue impedes full function, blocking blood supply and other vessels. Bleeding of varices, hepatic encephalopathy, ascites, jaundice, gall stones, oily stools
End stage cirrhosis: Liver function severely impacted to point of failure. More severe symptoms - confusion and neurological problems
What are the histological characteristics of a normal liver biopsy?
Central nucleus
Absent cell swelling
Pink cytoplasm
What are the cellular histological features of a liver biopsy in a patient with ALD? 5
Fat droplets displace cell nucleus
Hepatocyte ballooning = cell damage = fibrosis
Pale, bubbly cytoplasm
Inflammation (hepatitis)
Sclerosing hyaline necrosis - mallory denk bodies (pink)
Is ALD reversible? 3
If stop drinking, damage of lipid accumulation can be reversed. ALT levels and fat droplet levels will fall
If continue to drink - extensive cellular injury, irreversible cell death - Cirrhosis, acute liver failure
Exact point of irreversibility is not defined
Explain the histological changes in ALD (cellular, and bigger picture) (4)
- Micro and macro vascular steatosis extends from central vein to zone 2 of lobule
- Damage most to zone 3, as has the worst blood supply
- Hepatocyte cell ballooning - swells to several times normal size - form of parenchymal cell death
- Mallory denk bodies linked to sclerosing hyaline necrosis - both fibrosis and necrosis occurs
Apoptosis vs necrosis
Necrosis =
passive ‘accidental’ cell death
Not controlled, messy
Typically after injury and not a physiologicl process
Usually involves large group of cells
Apoptosis =
Physiological process
Enzymes break down cells - neat and tidy
Usually involves only single cell
How is steatosis as a stage of liver disease identified histologically?
First response of liver to alcohol abuse
Accumulation of fats (triglycerides, phospholipids, cholesterol esters)
How is alcoholic steatofibrosis of the liver identified histologically?
Ballooning hepatocyte and inflamed fatty liver
Steatofibrosis begins with perivenular fibrosis that extends outward along the sinusoids. Primarily initially in space of disse
How is fibrosis of the liver identified histologically?
Excess accumulation of collagen - shows blue - and other ECM proteins. Fibrous scars
How is cirrhosis of the liver identified histologically?
Can lead to a form of apoptosis
Excess fibrous tissue -> parenchymal (organ tissue) nodules
What are the distinguishing factors histologically between ALD and NAFLD?
ALD:
Sclerosing hyaline necrosis
Fibro-obliterative and inflammatory lesions of outflow veins
Alcohol foamy degeneration (extensive microvascular steatosis in perivenular areas)
Acute cholestasis (stagnation or marked reduction in bile secretion and flow)
What are the stages from which are reversible and from which liver transplant or death is likely?
Reversible stages: simple steatosis, alcoholic hepatitis, alcoholic liver hepatitis
Alcohol associated cirrhosis and hepatocellular carcinoma are end stages and result in death and liver transplants are needed
What is the normal level of fat in a healthy liver?
Fat in <5% of hepatocytes
What is the eligibility criteria for a liver transplant?
2 criteria:
- without transplant it is highly likely your expected lifespan is shorter than normal OR QoL is so poor, it is intolerable
- Expected that you have at least 50% chance of living at least 5 years after the transplant with acceptable QoL
Who cant receive a liver transplant/wont be given it?
Severe malnutrition and muscle wasting
Current infection
AIDS
Serious heart/lung condition
Mental health condition that would impact ability to follow recommendations after transplant
Advanced liver cancer - too late
What is the function of albumin?
- Maintains blood volume by maintenance of appropriate osmotic pressure - prevents fluid leaking into tissue due to large size and negative charge
> Large molecules exert osmotic pressure, draws water in
> Balances the opposing hydrostatic pressure (pushes fluid out vessels) and osmotic pressure (draws water in) - Carrier protein - binds to and transports different molecules around bloodstream, neutralises free radicals
What happens to albumin levels during liver damage, and what are the effects?
Albumin production decreases
Leads to reduced oncotic pressure in blood vessels - fluid leaks out into tissues - causes ascites and oedema
Summarise the RAAS system (6)
Liver produces angiotensinogen
Renin released from the kidneys due to fall in blood pressure or fluid volume
Renin converts angiotensinogen into angiotensin I
ACE released from the lungs converts angiotensin I to angiotensin II
> Angiotensin II acts on adrenal gland to stimulate release of aldosterone which causes NaCl and water reabsorption in kindeys
> Angiotensin II acts on blood vessels causing vasoconstriction
What effect can liver damage have on blood pressure?
- Reduces angiotensinogen production from liver > reduces angiotensin I and II levels > decreased blood pressure regulation > hypotension
Other than blood pressure, what other effects on the blood does liver damage have? **
Imbalances in regulation of fluids and electrolytes
> Hyponatremia (low sodium)
> Hypokaleamia (low potassium)
This affects BP and blood volume
Decreased aldosterone metabolism - regulates sodium conc
Reduced bile production - vit D regulates calcium and sodium balance
Impaired potassium regulation
Ineffective detoxification
What are the physiological effects of stress of the GI tract? 7
- Hypothalamus releases CRH to anterior pituitary gland binds to receptors in the gut and brain, function in peristalsis, secretion and mucosal barrier of GI
- Anterior pituitary gland release ACTH to adrenal gland
- Adrenal gland releases cortisol > increases BF to gut > stomach cramps
- CRH can induce mast cell deregulation and increase mucosal permeability
- Stress also activates SNS which releases catecholamines causes inflammation
- Stress inhibits vagus nerve which has anti-inflammatory effects
What GI symptoms can stress cause? 5
Slows or speeds up digestion
Bloating
Abdominal pain
Constipation/diarrhoea
Loss of appetite
What are the symptoms of liver failure? (8)
- Development of liver cirrhosis
- Jaundice
- Ascites
- Spider naevi
- Gynaecomastia
- Palmar erythema
- Splenomegaly
- Oesophageal varices
- Effect of alcohol withdrawal
What are the symptoms and effects of liver cirrhosis? 12
- 40% with cirrhosis are asymptomatic until late stages, have non-specific manifestations: weight loss, weakness, N&V
- Cirrhosis increases hepatic vascular resistance > portal hypertension leads to complications:
> spider naevi
> gynaecomastia
> splenomegaly
> caput medusae
> ascites
> testicular atrophy
> pitting ankle oedema
> jaundice
> muscle wasting
>bruising
What are spider naevi and why do they appear with liver cirrhosis?
Dilation of end vasculature under the skin surface, carrying free flowing blood.
Central red spot with radiating vessels
Pathophysiology unknown but potentially due to increased growth factors for angiogenesis, or hyperestrogenism due to liver damage.
What is gynaecomastia and why does it occur in liver cirrhosis patient?
Enlargement of the breast tissue in men
- Liver metabolises and regulates hormones including testosterone and oestrogen
> leads to accumulation of oestrogen (reduced metabolism) > breast tissue and testicular atrophy
> decreased testosterone production as HPG axis disrupted by cirrhosis
