Clinical Aspects of Neoplasia Flashcards
how can neoplasms lead to pressure effects or obstruction?
Neoplasms occupy space alongside normal tissues
Even a benign neoplasm can be life threatening
compress vital organs
Cancers arising within or metastatic to an endocrine gland may cause?
an endocrine insufficiency by destroying the gland.
What are the complications of Neoplasms in the gut?
both benign and malignant, may cause obstruction as they enlarge.
Infrequently, this may lead to intussusception
Malignant neoplasms of the gastrointestinal tract are often associated with iron deficiency anaemia.
what is the result of nerves being invaded?
pain
what is the result of blood vessels being invaded?
local haemorrhage
what is the result of mucosal membranes being invaded?
significant blood loss
What is Cancer Cachexia?
Ongoing loss of skeletal muscle mass (with or without loss of fat mass) which leads to progressive functional impairment.
what is the Overall % prevalence of weight loss in cancer patients?
may rise as high as 86% in the last 1 2 weeks of life.
What is the prevalence of cachexia in advanced cancer?
Published data reports from 60% to 80%
Estimates of cancer cachexia indicate that this syndrome may directly contribute to what % of cancer deaths?
30%
More than 50% of patients with cancer die with cachexia present
MECHANSIMS OF CACHEXIA?
How is Intestinal malabsorption caused in cancer patients?
Mechanical limitations (e.g. difficulties in swallowing, feelings of saturation, nausea)
restrict energy uptake and recovery in patients with gastrointestinal cancer.
Weight loss occurs in up to 83% of patients with upper gastrointestinal malignancy.
How is Cachexia due to chronic heart failure caused?
is thought to result from mesenteric ischemia and disturbed microcirculation of the intestine.
How do Chemotherapies contribute to cachexia
thought to contribute to the development of intestinal absorptive dysfunction.
how are glucose and lipid transporters involved?
Alterations in expression or localization of the major intestinal glucose (SGLT1, GLUT5, GLUT2) and lipid (CD36, NPC1L1, SRB1) transporters are likely.
Altered intestinal gluconeogenesis may further contribute to the energetic imbalance.
importance of gut microbiota in health?
Healthy energy metabolism is modulated by the amount and species of gut microbiota.
Gut microbiota influences the regulation of bile acids and cholesterol metabolism.
when do Gut barrier dysfunction and endotoxemia occur?
when the intestinal mucosal barrier leaks or breaks down.
Gut microbiota or bacterial cell wall components enter the circulation and cause an inflammatory response (cytokine production, altered levels and activation of T cells).
Increased bacterial translocation is associated with worse prognosis.
what is Ghrelin involved in?
the regulation of appetite, gut motility and gastric acid secretion.
also involves in white and brown adipose tissue function and glucose metabolism.
why Ghrelin may be closely linked to anorexia?
Ghrelin levels are elevated upon fasting
The increased ghrelin levels fail to induce appetite and energy storage (ghrelin resistance)
Other gut hormones, GLP‐1 and GIP, have less well‐defined roles.
The role of increased ghrelin levels in cachexia?
fail to induce appetite and energy storage (ghrelin resistance)
Other gut hormones, GLP‐1 and GIP, have less well‐defined roles.
Why are bile acids important?
metabolic regulators
Bile acids are not only important for digestion and fat absorption
but are also involved in the regulation of appetite and food intake.
Bile acids stimulates the secretion of what?
glucagon like peptide 1 (GLP‐1) and hormone peptide YY (PYY)
and increases the feeling of fullness
how do Bile acids induce energy expenditure?
by promoting intracellular thyroid hormone activation
via type 2 iodothyronine deiodinase (D2),
which converts inactive T4 into active T3.
proven in mice
The fat malabsorption seen in patients with cachexia hints toward …?
lower bile acid levels in wasting.
what are Futile cycles?
Mechanisms to regulate and fine‐tune metabolic processes under physiologic conditions.
Futile cycles in in cachectic conditions?
Increased and the released metabolites are involved in inter‐organ cycles.
Lactate derived from tumours is reconverted to glucose via hepatic gluconeogenesis.
Hepatic gluconeogenesis can also be fuelled by amino acids derived from muscle protein degradation.
Name the Cellular compartments?
cytosol, ER, Golgi apparatus, lysosomes, mitochondria, nucleus, and peroxisomes.
What does energy wasting in the liver under cachectic conditions lead to?
a reduction in the oxidative phosphorylation capacity of mitochondria.
Other hepatic involvement?
Decreased usage of hepatic triglyceride stores has been demonstrated in cancer cachexia.
Hepatic steatosis is a prerequisite of non alcoholic fatty liver disease and is associated with sarcopenia (muscle loss).
muscle role in starvation?
serves as a protein reserve for energy production during starvation.
Muscle accounts for up to 40% of body weight, accounting for 20 30% of total resting energy expenditure.
which Inflammatory mediators play a crucial role in muscle atrophy?
such as IL‐1b, IL‐6, and TNFα