Week 5 Flashcards
1
Identify and explain the clinical manifestations of NAFLD.
1 A
Explain how insulin resistance can lead to the development of hepatic steatosis.
-In individuals with established insulin resistance and metabolic syndrome, the visceral adipose tissue not only increases, but also becomes dysfunctional, with reduced production of the lipid hormone,adiponectin, and increased production of inflammatory cytokines such as TNF-α and IL-6.
Explain how hepatocellular oxidative injury can result in hepatic inflammation and necrosis.
- visceral adipose tissue increased production of inflammatory cytokines such as TNF-α and IL-6 which promote hepatocyte apoptosis.
- Diminished autophagy also contributes to mitochondrial injury and formation of Mallory-Denk bodies. Kupffer cell production of TNF-α and TGF-β activate stellate cells directly leading to deposition of scar tissue ( Fig. 18-5 ). Stellate cell activation also occurs through the hedgehog signaling pathway in part through natural killer T-cell activation. In fact, the level of hedgehog pathway activity correlates with stage of fibrosis in NAFLD.
common comorbidities of NAFLD
ncluding obesity, dyslipidemia, metabolic syndrome, diabetes.
significance of elevated AST and ALT levels.
- AST is higher in OH induced
- Hepatocyte integrity is compromised, there is hepatocyte damage.
HCC and NAFLD
NASH also increases the risk of hepatocellular carcinoma as do other metabolic diseases.
Lifestyle recommendation for NAFLD
- ○ Reduced consumption of saturated animal fats and high fructose simple sugars
- Exercise
Utility of Vit E in NAFLD
- hepatoprotective effects
- caution in patients taking anticoagulants, as chronic high dosing may affect blood clotting
Supplements and herbs in NAFLD
- omega-3 fatty acids : improve postprandial lipoprotein metabolism by decreasing triglycerides and increasing HDL-cholesterol
- Milk thistle role in maintaining normal glucose and lipid metabolism
utility and adverse effects of pioglitazone
- potent peroxisome proliferator-activated receptor-gamma
- increases insulin-dependent glucose disposal and decreases hepatic glucose output by decreasing insulin resistance
- edema, increased weight
clinical features of celiac disease
- Diarrhea, Flatulence, Weight loss, Severe abdominal pain
- anemia
pathophysiology celiac disease
- tissue transglutaminase deamidates glutamine into gliadin which induces interleukin 15 in the enteric epithelial cells causing intraepithelial lymphocytes to express NK-G2D, a marker for natural killer T lymphocytes.
significance of fecal fat in the stool with celiac disease
- Absence of intestinal villi and lengthening of the intestinal crypts
Importance of zonulin
- zonulin: opens up the spaces between the cells of the intestinal lining which is increased bc of gliadin
Characterize the innate and adaptive immune response to gliadin
- gliadin presented by the HLA molecules to helper T cells.
- THF help in formation of autoantibodies to type 2 transglutaminase (TG2)
- TH1 release cytokines causing lymphocyte infiltration leading to destruction of the absorptive surface
