Insulin, altered cell bio, and cancer Flashcards
If someone is obese what should you not assume and why?
That the person is unhealthy, because 20% of obese persons are healthy
How are insulin levels related to fat gain?
They are both a cause and consequence of fat gain.
Obesity leads to insulin resistance and myraid other health problems, list some.
Polycystic ovarian syndrome, hypertension, sarcopenia, steato hepatitis, cancer, atherosclerosis….
What percentage of overweight or obese persons in the US are IR/diabetic?
Over 50%
What are the names of the two great Canadians who first purified insulin?
Fred Banting and Charles Best
What is insulin and where is it made?
small peptide hormone made in pancratic beta cells
What are three ways you can increase your blood glucose naturally?
1) 111111Uptake from the intestines Reabsorption in the kidneys Release from the liver
How is glucose transported in the kidney and gut and through what type of cells does it cross?
Through sodium-glucose symport (SGLT) into the epithelial cells. Glucose is transported against its concentration gradient by Na+ which moves down its gradient. This symporter is not required for glucose movement into the blood.
How might a lack of sodium affect glucose uptake or reabsorption in the body?
Glucose uptake is directly affected by the functionality of the SGLT symporter which requires sodium to function, without adaqate amounts of sodium glucose would either be moderatley or severly inhibited from entering the blood stream. In this state the liver would likely release glucose, or a hypoglycemic state may occur.
Whats the most common way in which glucose enters cells from the blood stream and are any of these processes regulated by insulin?
Glucose typically enters cells via glucose transporters. There are 13 of them but only GLUT4 is regulated by insulin.
In what tissue types is the GLUT4 transporter found?
Skeletal muscle, cardiac muscle, and adiposites
When is insulin acutely high?
After a meal, post prandial. Acute NOT CHRONIC!
Are insulin levels high in pre-diabetics?
YES unfortunatley physicians typically check glucose levels and not insulin though, so this is rarley a diagnosis even though a large number of people are pre-diabetic.
How is insulin regulated by the sympathetic and parasympathetic nervous systems?
Sympathetic: Increase glucagon Decrease Insulin Parasympathetic: Increases Insulin Decreases Glucagon
What affects does insulin have on the liver, skeletal muscle, and adipocytes?
Liver: Inhibits ketogenesis, stimulates glucogenesis, and lipogenesis. Skeletal muscle: Stimulates Anabolism, Adipocytes: stimulates lipogenesis, and adipogenesis.
Insulin reduces what 3 important molecules from the blood?
Blood:glucose, fat, and ketones
Under what conditions would someone get ketoacidosis, and why?
Insulin insensitivity (diabetes) or type 1 diabetes where no insulin is produced, because insulin suppresses the formation of ketones in the liver,
what is the primary regulator of insulin and glucagon release?
blood glucose
How do insulin and glucagon regulate each other, in which cells are they produced?
insulin directly inhibits glucagon and is produced in pancreatic beta cells, whereas glucagon directly and indirectly stimulates insulin and is produced in pancreatic alpha cells.
glucagon affects the liver, skeletal muscle, and adipocytes in what ways? How is blood concentration of glucose, fat, and ketones affected?
It stimulates glycogenolysis, gluconeogenesis, and ketone formation in the liver, no affect in skeletal muscle, and lypolysis in the adipocytes. Overall blood glucose, fat, and ketones increase as a result.
How will the consumption of carbs, protein, and fat affect the hormones insulin and glucagon and what will be the net result?
Carbs will increase insulin a lot and decrease glucagon leading to fat gain, proteins will increase insulin some and also increase glucagon leading to muscle growth, and fat consumption will lead to neutral insulin and increased glucagon and fat loss.
what are 5 major problems associated with insulin levels being too high?
- hypoglycemia 2. Low glucagon 3. Reduced ketogenesis 4. Reduced lypolysis 5. CNS starvation
when would the body have excess insulin?
- pancreatic tumor in the beta cells, 2. injection, 3. Diabetic
what is anaplasia? What do you call the associated size and shape variation among these cells?
absence of differentiation. Pleomorphic
What is metaplasia, dysplasia, and hyperplasia?
Meta: Replacement of one cell type with another that is typcally less differentiated.
Dys: Loss of normal cell organization.
Hyper: Increased cell growth
What problems do Ischemia and anoxia lead to on a cellular level?
Decrease in ATP, Failure of Na+,K+ , Ca2+pump= cellular swelling.
Reperfusion injury: Reactive oxygen species
What are some blunt force tissue injuries one could sustain; define them?
Contusions (deep) and hematomas (more superficial)
Abrasion–scrape
Laceration–Tear
Fracture
Name 4 sharp force injuries
Incised wound: L than D
Stab: D than L
Puncture: Sharp point, not edge
Chopping: combo blunt and sharp
Name 3 immunologic and inflammation injuries
Phagocytic cells: can damage host tissues
Immune and inflammatory substances: Histamine, antibodies, cytokines, complement, and enzymes
Membrane alterations: permeability changes
Hyper-thermia what are the three phases from minor to severe?
Heat cramps (voluntary muscles)
Heat Exhaustion: High hematocrit concentration as a result of water loss. Hypovolemia (low blood volume)
Heat Stroke: Soft tissue failure, Hypotension/volemia
Radiation injuries usually have the most damaging effect on which type of cells? Name three specific types
Rapidly dividing cells
GI
Fetus
Bone marrow
Cells can be injured through the accumulation of infiltrates such as? What are some manifestations of these injuries? Why can this be harmful?
water, lipids, carbs, glycogen, proteins
Pigments (melanin) Ca 2+ (heart) Urate (joints)
This can change osmotic gradients in a negative way
How is necrosis different from apoptosis?
Necrosis promotes local inflammation because it’s not a neat and clean death, the cell is ruptured and nuclear debris is released etc. Apoptosis is neat.
What is hydropic degeneration?
When a cell loses the ability to regulate ion permeability due to an INJURY, and receives an influx of infiltrates leaded to cellular damage.
This can lead to hypertrophy, gout, ect but these are causes, not a definition.
Name 5 types of tissue necrosis and the most common tissue associated with each?
How do you treat it?
Coagulative: Kidney, heart, spleen, glands (looks opaque)
Liquefactive: Brain (slimy)
Caseous: Lung (cottage cheese)
Fat: Pancreas, breast, abdominal organs (saponification/white)
Gangrenous: limbs. Dry crusty, wet smelly, and Gasy
Treatment: Revascularization, treat the infection
What are the 4 major postmortem changes in somatic death?
Algor mortis: low temp
Livor mortis: blood settling to lower tissues
Rigor mortis: muscle stiffness
Postmortem autolysis: lytic dissolution of cells/tissues
Adipocyte number is mostly set by what age? This means that the further development of these cells is less likely after this point.
Does adipocyte number determine obesity?
2yrs old
NO. A person can have a small number of large adipocytes or a large number of small adipocytes, it just depends.
Most fat LOSS is the result of what? When does hyperplasia of adipocytes occur in adults?
Adipocyte shrikage
If a person is 170% above their BMI
What is a typical hematocrit level for men and women?
Men 45 and women 40
In what type of climate is salt and water loss more prevalent and why?
Arid climate because the dry air allows for increased evaporation compared to a humid climate.
What are some factors that influence adipocyte number and potential obesity?
Gestational birth weight
Maternal insulin
In Utero toxin exposure
What are the five characteristics of a benign tumor? Remember that they are the exact opposit of a malignant tumor.
1) Slow growth/low mitotic index
2) Well-defined capsule (malignant no capsule)
3) Well differentiated
4) Not invasive
5) No metastasis
What is an Adenocarinoma and how is it different from an Adenoma?
What is a sarcoma?
Adeno-cancer of duct or gland
Carcinoma- Malignant epithelial tumor
Adenoma- is a benign dut or gland tumor
Sarcoma- malignant tumor in connective tissue
What are some characterisitcs of a transformed cancerous cell?
Independent of normal cellular controls (oncogenes active, or p53 disregulation)
Anchorage independent (it can move)
Immortal
Anaplasia/pleomorphic
How can gene amplification increase ones risk for cancer?
Name 3 common proto-oncogenes
If you’re overexpressing a proto-oncogene it will act as an oncogene and disregulate cellular processes related to cell growth and death.
ras, Rb, p53
Explain the interaction between ras, RB and p53, and why they are considered proto-oncogenes?
p53 and Rb are tumor suppressor genes, so when mutated they may fail to suppress tumors. They can also be turned off by a constitutively active ras gene which naturally inhibits them, when ras has been mutated in a manner which leads to permanently active state.
What are 4 ways in which cancer cells stimulate or maintain growth?
Secretion of growth factors (autocrine)
Increased number of GF receptors
Receptor mutated to a permanent ON position
Activation of protein kinases that drive the cell cycle
What is typically more dangerous a melanoma or a basal or squamous cell carcinoma?
Melanoma (mole)
How does physical activity reduce your risk of cancer?
Decreased insulin (growth signal) and associated growth factors, obesity, inflammation and free radicals
Increase gut motility (how does this help?)
Why does being obese increase your risk for cancer?
Because adipocytes are active endocrine tissues that secrete VEGF and TNFalpha. VEGF stimulates angiogenesis which can feed hungry cancer cells larger than 1mm, and TNFalpha is a pro inflammatory cytokine.
Also increased insulin because it elicits growth signals and tumors like to increase the number of receptors they have for insulin as a result
What is the Warburg Effect? What does this have to do with a ketogenic diet?
Cancer cells prefer glucose as an energy source
Some studies have shown that using ketones instead of glucose for energy decreases insulin and starves cancer cells!
What is the greatest risk factor for developing mutations that could lead to cancer?
Age
True or False. Metastasis is possible for all cancer types?
False
What is the three step theory of invasion when speaking of cancer cell metastasis?
1) Attachment (decrease fibronectin increase laminin) 2) Degrading of the matrix (enzymes) 3) Moving into the matrix (linvadopodia)
What is organ tropism?
Preferential growth of cancer cells in certain organs
What are the 4 stages of cancer and what are they based on?
1) Cancer is confined in the organ or origin 2) Locally invasive 3) Regional structures 4) distant sites The staging of cancer about size invasion and spread.
Where can tumor cell markers be found in the body? What types of substances are these? What is their clinical significance?
Blood, CSF, cell membrane, urine. Hormones, enzymes, genes, antibodies. They are useful in screening, diagnosing, and observing treatment
What is cachexia what percentage of cancer patients experience it?
Severe form of malnutrition, 80% of cancer patients experience it.
Explain the relationship between anemia and Hepcidin?
Anemia is the result of a decrease of available iron containing hemoglobin in the blood. Hepcidin regulates iron in the body and can bind iron in the gut and in macrophages preventing its absorption and use in hemoglobin which can be partially responsible for an anemic state.
What are the effects of a tumor invasion in bone marrow?
Leukopenia and thrombopenia result which can lead to increased host infection. Chemotherapy is toxic to bone marrow which makes fighting a tumor of this type difficult.
How do you end up dying from cancer?
infection, hemorrhage, blood clots, anemia, loss of organ function
What type of chemotheraputic agents are used in chemotherapy, and what is the goal of this treatment? What are neoadjuvant chemotherapies?
Non-selective cytotoxic drugs, target both normal and malignant cell growth. These can be single drugs or combinations. The goal is to eliminate as much cancer as possible and hope the immune system can cope with the rest. Preventative chemo before surgery to remove a tumor to prevent micrometastatic spread
What is a Euploid cell and how is it different from a polyploid cell?What is aneuploidy, and how does it typically occur?
A Euploid cell has a normal number of haploid and diploid chromosomes where as polyploid is some multiple of the norm. Aneuploidy is when a somatic cell does not contain a multiple of 23 chromosomes. This is usually the result of non-disjunction.
How is Sorbitol generated in diabetics and why is it a problem?
Sorbitol is a reduced form of glucose that accumulates in cells when glucose levels are high and it can not readily go through glycolysis. The accumulated sorbitol increases cell osmolarity leading to cellular damage
