7: Obesity Flashcards
1
Q
Define NAFLD
A
- Non-alcoholic fatty liver disease
Presence of hepatic steatosis (fatty liver) in individuals who do not consume alcohol or do so in small quantities and who do not have another cause of secondary hepatic fat accumulation - HCV, Wilson disease, medications - Diagnosis of exclusion
2
Q
Conditions associated with NAFLD
A
○ Type 2 diabetes mellitus ○ Overweight/obesity ○ Hyperlipidaemia ○ Hypertension ○ PCOS ○ Hypothyroidism
3
Q
What is the difference between NAFLD and NASH?
A
- NASH is a type of NAFLD
- Non-alcoholic steatohepatitis
○ Steatohepatic injury
○ Fibrosis and cirrhosis
○ Histologically similar to alcoholic hepatitis
- Non-alcoholic steatohepatitis
4
Q
Pathology of NAFLD
A
- Precise mechanisms unknown
- Strong association with insulin resistance
- Insulin resistance leads to increased release of free fatty acids from adipocytes due to overactivity of lipoprotein lipase.
- reduced production of adiponectin from adipocytes
- decreases oxidation of free fatty acids by skeletal muscle and increases free fatty acid uptake in hepatocytes
Hepatocytes down-regulate lipolysis,
Fat-laden cells are highly sensitive to lipid peroxidation products generated by oxidative stress, which can damage mitochondrial and plasma membranes, potentially leading to apoptosis or necrosis
- decreases oxidation of free fatty acids by skeletal muscle and increases free fatty acid uptake in hepatocytes
- Dysfunctional adipocytes synthesise pro-inflammatory cytokines such as TNF-a.
- Once cell injury becomes established, release of cytokines such as TNF-a locally from Kupffer cells leads to the activation of stellate cells, collagen deposition, and scarring
High fructose diets have also been associated with increased risk of NAFLD-related fibrosis, and dietary fat, particularly trans-fat, may have a role in producing liver injury.
Obstructive sleep apnoea has been associated with disease progression, possibly related to intermittent hypoxia
Fibrosis may be accelerated when injury from another liver disease (e.g., haemochromatosis) is superimposed on NAFLD.
5
Q
Describe and illustrate the morphology of NAFLD and NASH.
A
- NAFLD
○ Hepatic steatosis - yellow enlarged appearance gross
○ Lipid droplets microscopically- NASH
○ Fibrosis around central vein - fine spider wed of pericellular collagen deposition
○ Ballooned hepatocytes
○ Mallory-Dank bodies - complex of misfolded cytoskeletal elements
- NASH
6
Q
What are the consequences of disease progression of NAFLD
A
- Hepatic complications: ○ Liver fibrosis and cirrhosis ○ Portal hypertension ○ Variceal haemorrhages ○ Hepatocellular carcinoma ○ Liver transplant - Others: - Increased risk of ○ Type 2 diabetes (2-fold increase) ○ Hypertension Chronic kidney disease
7
Q
What is the pathogenesis of acute cholecystitis?
A
- 90% of cases caused by obstruction of neck of gallbladder or cystic duct by a stone
- Chemical irritation and inflammation of gallbladder obstructed by stones
- Mucosal phospholipases hydrolyses luminal lecithins to toxic lysolecithins
- Normally protective glycoprotein mucus layer is disrupted exposing mucosal epithelium to detergent action of bile salts
- Prostaglandins released contribute to mucosal and mural inflation
- Distention of gallbladder and increased intraluminal pressure compromise blood flow to mucosa
- Initially occur in absence of bacterial infection but later bacterial infection may be superimposed and exacerbate inflammatory process
8
Q
Morphology of cholecystitis
A
- Gross
○ Enlarged and tense gallbladder
○ Bright red or blotchy, violaceous to green-black discolouration imparted by subseral haemorrhages
○ Serosa covered by fibrinous exudate
○ Obstructing stone present in neck of gallbladder of cystic duct
○ Gallbladder lumen contains more stones
○ Filled with cloudy, or turbid bile mixed with fibrin, pus and haemorrhage
○ Gallbladder empyema - exudate pure pus
○ Gangrenous cholecystitis - green-black necrotic organ with perforations- Histologically
○ Early changes
§ Oedema
§ Congestions
§ Mucosal erosion
Neutrophils sparse unless superimposed infection
- Histologically
9
Q
Clinical features of cholecystitis
A
- RUQ or epigastric pain
- Associated with
○ Mild fever
○ Anorexia
○ Tachycardia
○ Sweating
○ N+V
- Associated with
10
Q
In what circumstances may an individual suffer cholecystitis in the absence of gallstones?
A
- Acute acalculous cholecystitis
- Ischaemia
- Cystic artery end artery without collateral circulation
- Risk factors
○ Sepsis with hypotension and multisystem organ failure
○ Immunosuppression
○ Major trauma and burns
○ Diabetes mellitus
○ Infections
11
Q
What is the pathogenesis of chronic cholecystitis?
A
Sequel to repeated bouts of mild to severe acute cholecystitis or develops in absence
12
Q
Morphology of chronic cholecystitis
A
- Gross ○ Subserosal fibrosis ○ Dense fibrous adhesions ○ Wall thickened ○ Opaque grey-white appearance - Histological ○ Scattered lymphocytes, plasma cells and macrophages in mucosa and subserosa fibrosis tissue ○ Marked subepithelial and subserosa fibrosis with mononuclear cell infiltration
13
Q
Clinical features of chronic cholecystitis
A
- Recurrent attacks of either steady epigastric or RUQ pain
- N+V
Intolerance to fatty foods
- N+V
14
Q
What complications can arise from acute and chronic cholecystitis?
A
- Bacterial superinfection with cholangitis or sepsis
- Gallbladder perforation and local abscess formation
- Gallbladder rupture with diffuse peritonitis
- Biliary enteric (cholecystenteric) fistula, with drainage of bile into adjacent organs, entry of air and bacteria into the biliary tree, and potentially, gallstone-induced intestinal obstruction (ileus)
- Aggravation of pre-existing medical illness, with cardiac, pulmonary, renal, or liver decompensation
15
Q
Classification of gallstones
A
- Cholesterol gallstone
○ Western populations
○ Located in gallbladder
○ 10-20% radiopaque
○ Mostly cholesterol- Mixed gallstones
- Pigment gallstones
○ Non-western populations
○ Located in gallbladder (black) and large bile ducts (brown)
○ 50-75% of black are radiopaque and all brown are radiolucent
○ Consist of calcium, phosphate, bilirubin and bile acid
16
Q
Risk factors for cholesterol gallstones
A
§ Gall bladder hypomotility □ Vagotomy □ Octreotide □ Prolonged fasting § Supersaturated bile □ Increased age □ Female □ Genetics □ Obesity □ Drugs □ Diet □ Liver disease □ Pregnancy § Mucin hypersecretion □ Infection § Decreased bile salt excretion □ Bowel transit time □ Ileal resection □ Crohn's □ Cholestyramine □ Faecal flora
17
Q
Pathogenesis of cholesterol gallstones
A
○ Pathogenesis
§ Soluble micelles
§ Nucleation into solid crystals when bile is supersaturated
§ Crystals trapped by mucus to form macroscopic stones
18
Q
Risk factors for pigment gallstones
A
□ Haemolysis □ Ineffective erythropoiesis □ Mucin hypersecretion ® Infection □ Gallbladder hypomotility ® Vagotomy ® Octreotide ® Prolonged fasting
19
Q
Risk factors of pigment gallstones
A
Black pigment stones □ Haemolysis □ Ineffective erythropoiesis □ Mucin hypersecretion ® Infection □ Gallbladder hypomotility ® Vagotomy ® Octreotide □ Prolonged fasting Brown pigment stones □ E.coli infection □ Lumbricids □ C.sinensis □ Mucin hypersecretion ->Infection
