Flashcards in Path: Nutritional Diseases Deck (98):
What is kwashiorkor disease and what is its micro presentation as seen in the liver?
Protein starvation. Steatosis of the liver due to lack of proteins for lipoprotein synthesis. Lipids accumulate in the hepatocytes. Individuals with kwashiorkor still get adequate forms of energy from carbs, etc.
There are two differentially regulated protein compartments in the body: the ________ compartment, represented by proteins in skeletal muscles, and the ________ compartment, represented by protein stores in the visceral organs, primarily the liver.
somatic compartment; visceral compartment
Which protein compartment is depleted more severely in marasmus (inadequate energy intake of all forms, pt looks emaciated).
Which protein compartment is depleted more severely in kwashiorkor?
A child is considered to have marasmus when weight falls to ___% of normal for sex, height, and age.
Describe the physical appearance of a marasmic child and why they look that way.
A marasmic child suffers growth retardation and loss of muscle, the latter resulting from catabolism and depletion of the somatic protein compartment. This seems to be an adaptive response that provides the body with amino acids as a source of energy.
Describe the serum albumin levels of a marasmic child.
Serum albumin levels are either normal or only slightly reduced because the visceral compartment, which is presumably more precious and critical for survival, is only marginally depleted.
What else, besides muscle proteins, is mobilized and used as fuel, contributing to the emaciated appearance (ribs showing, bones accentuated, head appears too large for body)
In marasmus, leptin is low (now you know), so what causes mobilization of subcutaneous fat stores?
Stimulation of the hypothalamic-pituitary-adrenal axis to produce high levels of cortisol that contributes to lipolysis.
Immune deficiency is also found in pts with marasmus, particularly ___-cell mediated immunity.
Even though protein is found in the diet, less severe forms of kwashiorkor may be found in pts with this condition in which protein is not absorbed.
Hypoalbuminemia will be seen in kwashiorkor or marasmus?
Loss of weight in individuals with less severe forms of kwashiorkor is masked by:
increased fluid retention and edema into extravascular spaces due to hypoalbuminemia
Besides a swollen belly, what other signs may you look out for in pts with kwashiorkor?
alternating zones or hyper/hypopigmentation, areas of desquamation, giving a "flaky paint" appearance.
Hair changes include overall loss of color or alternating bands of pale and darker hair.
Apathy, listlessness, and loss of appetite.
Is there edema in pts with marasmus?
Describe the appetite in pts with kwashiorkor.
Describe the appetite in pts with marasmus
Describe the anemia present in pts with marasmus and kwashiorkor.
Marasmus: Present, less severe
Kwashiorkor: Severe (sometimes)
Describe levels of subcutaneous fat in pts with kwashiorkor and marasmus.
Kwashiorkor: Reduced but present
Describe fatty infiltration of the liver in pts with kwashiorkor and marasmus.
_______ is self induced starvation, resulting in marked weight loss.
_______ is a condition in which the pt binges on food and then induces vomiting.
_________ has the highest death rate of any psychiatric disorder.
Amenorrhea, resulting from decreased secretion of ___________ (hormone), and subsequent decreased secretion of _______ (hormone) and _______ (hormone), is so common that its presence is considered a dx feature of anorexia and bulimia.
gonadotropin-releasing hormone (GRH); luteinizing hormone (LH); follicle-stimulating hormone (FSH)
Decrease in release of this hormone, found in anorexia and bulimia, can cause cold intolerance, bradycardia, constipation, and changes in the skin and hair.
Describe the changes in bone density found in anorexia and bulimia and why they occur.
Bone density is decreased, most likely because of low estrogen levels, mimicking the postmenopausal acceleration of osteoporosis.
What is a major complication of anorexia and bulimia that can cause cardiac arrhythmia and sudden death?
Cachexia is a state of profound loss of lean body mass and fat due to cytokines, principally:
________ occurs in about 50% of cancer pts and is responsible for about 30% of cancer deaths.
What causes mortality in cachexia?
generally the consequence of atrophy of the diaphragm and other respiratory muscles.
List 2 mediators that contribute to cachexia in cancer pts.
Lipid-mobilizing factor- increases FA oxidation and proinflammatory cytokines such as TNF
Proteolysis-inducing factor and proinflammatory cytokines cause skeletal muscle breakdown through the ___________-induced activation of the ubiquitin proteasome pathway.
List the fat soluble vitamins necessary for health.
A, E, D, K
____-soluble vitamins are more readily stored in the body, but may be poorly absorbed in fat malabsorption disorders caused by disturbances of digestive functions.
Describe how Vitamins D, K & biotin (B7), and niacin (B3) are synthesized endogenously
D- precursor steroids and UV exposure
K & biotin- intestinal microflora
niacin- from tryptophan
List the 3 major functions of Vit. A.
Maintenance of normal vision, regulation of cell growth and differentiation, and regulation of lipid metabolism.
T/F: Vitamin A is a fat-soluble vitamin, meaning its absorption does not require bile, pancreatic enzymes, or any level of antioxidant activity in the food.
False. Its absorption does Requires bile, pancreatic enzymes, and some level of antioxidant activity in the food.
What transports Vit. A in the blood stream?
Where are 90% of the body's Vit. A reserves stored?
If Vit. A wants to be released from the liver to travel to peripheral tissues and enter them, what must happen?
Vit. A must be bound to Retinol Binding Protein (RBP), which is synthesized in the liver. Peripheral tissues will not take up Vit. A unless it is bound to RBP.
What receptor is Vit. A (retinol) looking for on cells of Ito in the liver for binding and entry/storage in the liver?
Lipoprotein E receptors.
Why is Vit. A important for vision?
It is a precursor to synthesis of pigments found in rods and cones whose isomerization, when hit by a photon, triggers a nerve impulse that travels from the retina to the brain.
Vitamin A deficiency causes what metaplasia?
Mucus secreting epithelium>>>keratinizing epithelium
Why can supplementation of Vit. A help reduce morbidity and mortality in children suffering from diarrhea?
Benefit may be related to maintenance and restoration of the integrity of the epithelium of the gut. (remember the metaplasia caused by Vit. A deficiency!)
How can infections reduce *bioavailability* of Vit. A?
By inhibiting retinol binding protein (RBP) synthesis in the liver. RBP needed to transport Vit. A from the liver to peripheral tissues.
Retinoids (Vit. A) are used clinically for the treatment of these two skin disorders:
Severe acne and certain forms of psoriasis
How is Vit. A used to treat acute promyelocytic leukemia?
Through its ability to bind to a PML-RARa fusion protein that characterizes this form of cancer. Binding induces differentiation and subsequent apoptosis of these cancer cells. A different isomer has been used to treat neuroblastoma.
One of the earliest manifestations of Vit. A deficiency is:
Impaired vision, particularly in reduced light (night blindness)
What is the major function of the fat-soluble vitamin D?
Maintenance of adequate plasma levels of Ca2+ and Phosphorus to support metabolic functions, bone mineralization, and neuromuscular transmission.
Besides from the endogenous synthesis of Vit. D (cholesterol + UV light), where else can we get Vit. D in diet?
Deep-sea fish, plants, grains.
The production of 1,25-dihydroxyvitamin D in the kidney is regulated by 3 main mechanisms:
1) hypocalcemia stimulates secretion of PTH which augments the conversion of 25-OH-D into 1,25-dihydroxyvitamin D by activating 1a-hydroxylase
2) hypophosphatemia directly activates 1a-hydroxlase, increasing the production of 1,25-dihydroxyvitamin D
3) Through a feedback mechanism, increased levels of 1,25-dihydroxyvitamin D down-regulate its own synthesis through inhibition of 1a-hydroxylase activity.
How does 1,25-dihydroxyvitamin D regulate plasma levels of Ca2+ and phosphorus?
It acts by binding to nuclear receptors present in most cells of the body. Signals transduced via these receptors regulate plasma levels of calcium and phosphorus.
How is Vit. D implicated in bone mineralization?
It stimulated osteoblasts to synthesize the calcium-binding protein osteocalcin, involved in the deposition of Ca2+ during bone development.
How does Vit. D stimulate absorption of Ca2+ in the intestine?
Acts as a transcription factor for a critical calcium transport channel in duodenal epithelium. Gene expressed: TRPV6
How does Vit. D stimulate reabsorption of Ca2+ in the distal tubules of the kidney?
Again, acts as a nuclear transcription factor for a critical calcium transport channel in tubular epithelium. PTH acts in the same way. Gene expressed: TRPV5
How do 1,25-dihydroxyvitamin D and PTH act in concert to increase plasma concentrations of Ca2+ and Pho?
Both enhance the expression of RANKL on osteoblasts that interacts with RANK on osteoclasts, activating them to resorb bone, releasing Ca2+ and Pho.
Describe the 4 mechanisms by which elevated PTH levels induce changes in plasma levels of Ca2+, Pho, and 1,25-dihydroxyvitamin D.
1) activation of renal 1a-hydroxylase, increasing the amount of active Vit. D and Ca2+ absorption.
2) increased resorption of Ca2+ from bone by osteoclasts
3) decreased renal Ca2+ excretion
4) increased renal excretion of phosphate
Big picture: plasma Vit. D ^^^, Ca2+ ^^^, Pho decrease
Net loss of Pho = impaired mineralization of bone = osteomalacia/rickets.
T/F: low levels of 1,25-dihydroxyvitamin D are associated with a 30-50% increase in the incidence of colon, prostate, and breast cancers.
Overdose of Vit. D can cause what pathology in children and adults?
metastatic calcifications of soft tissues such as the kidney in children.
Bone pain and hypercalcemia in adults.
Deficiency of Vit. C leads to these defects:
Poor vessel support results in bleeding tendency due to lack of collagen
Inadequate synthesis of osteoid in bone formation
Impaired wound healing due to lack of collagen
How does leptin help us lose excess adipose tissue?
Decreases desire for food intake.
Increases desire to exercise, increases energy expenditure and is thermogenic.
Leptin acts on what area of the brain, stimulating neurons that tell you to stop eating and inhibiting neurons that tell you to eat.
What would a loss of function mutation in the leptin system cause?
Early onset, Severe obesity (rare)
What is peptide YY?
A satiety signal released post-prandially by endocrine cells in the ilium and colon
What is Ghrelin?
A peptide hormone secreted by the stomach that stimulates appetite
The acruate nucleus in the hypothalamus processes and integrates neurohumoral peripheral signals and generates efferent signals. It contains two subsets of first-order neurons:
1) POMC (pro-opiomelanocortin) and CART (cocaine and amphatamine-regulated transcripts) neurons
2) neurons containing NPY (neuropeptide Y) and AgRP (agouti-related peptide).
These first order neurons communicate with 2nd order neurons in the hypothalamus
What do POMC/CART neurons enhance?
energy expenditure and weight loss through the production of anorexigenic a-melanocyte-stimulating hormone (MSH) and the activation of melanocortin receptors 3 & 4 (MC3/4R) in second order neurons. The 2nd order neurons are in turn responsible for producing factors such as TSH and corti-cotropin releasing hormone (CRH) that increases the basal metabolic rate and anabolic metabolism, favoring weight loss.
What do the NPY/AgRP neurons enhance?
Promote food intake (oxrexigenic effect) and weight gain, through the activation of Y1/5 receptros in secondary neurons. The secondary neurons then release factors such as melanin-concentrating hormone (MCH) and orexin, which stimulate appetite.
Knowing leptin's function and purpose, does it act on POMC/CART neurons or MPY/AgRP neurons? What effect does it have on one or both?
Knowing PYY's function, does it act on POMC/CART neurons or MPY/AgRP neurons? What effect does it have on one or both?
Knowing what ghrelin does, does it act on POMC/CART neurons or MPY/AgRP neurons? What effect does it have on one or both?
Obesity is defined as a BMI greater than or equal to:
A person is considered overweight if their BMI is greater than or equal to:
Are the BMI metrics (obesity at BMI 30 and up) universally efficacious?
No. For example, in a study comparing South Asian and European subjects, the mean BMI associated with development of an adverse metabolic profile was 21 in SA and 30 in Europeans.
What is obesity defined as for Asians?
BMI > 25
What is overweight defined as for Asians?
BMI > 23 and < 25
T/F: regardless of how a pt's fat is distributed above or below their waist, their risks for heart disease, T2DM, HT and dyslipidemia are the same.
False. More fat above the waist (central adiposity) = higher risk for M&M
Let's play "Do You Remember from 1st Semester?"
What are the 4 aspects of the metabolic syndrome? ONLY NEED 2 TO QUALIFY AS HAVING MS
1) diabetes mellitus
4) abdominal (above waist) obesity
The metabolic syndrome is a pro-inflammatory and pro-thrombotic state associated with elevated levels of this inflammatory protein, these 4 proinflammatory cytokines, and this inhibitor of fibrinolysis:
plasminogen activator inhibitor-1
__________ is an anti-inflammatory cytokine produced exclusively by adipocytes. Explain how it do.
Adiponectin enhances insulin sensitivity and inhibits many steps in the inflammatory process.
Describe why adiponectin is called the "guardian angel against obesity"
It directs FAs to muscle for oxidation. Decreases influx of FAs to the liver and total hepatic triglyceride content, and also decreases the glucose production in the liver, causing an increase in insulin sensitivity and protecting against the metabolic syndrome.
What type of diet does the metabolic syndrome respond well to?
1) Mediterranean diet (high in fruits, veggies, nuts, whole grains & olive oil)
2) Low sodium diet
3) Low glycemic index (whole grains to replace refined grains)
What is the minimum recommended amount of exercise, daily?
30 mins of moderate exercise (brisk walking)
Insulin resistance results in the accumulation of triglycerides in hepatocytes by at least 3 mechanisms:
Impaired oxidation of FAs
Increased synthesis and uptake of FAs
Decreased hepatic secretion of VLDL cholesterol
How do gallstones form?
When cholesterol concentrations exceed the solubilizing capacity of bile (its only way out), cholesterol can no longer remain dispersed and crystallizes out of solution. These are cholesterol stones, one type of gallstone. (makes of 80% of stones in the West)
What are the 4 risk factors for gallstones (cholelithiasis)? Hint: 4 Fs
Describe the Raynaud phenomenon.
An exaggerated vascular response to cold with abnormal vasoconstriction of digital arteries
The fingertips in Raynaud phenomenon go from white>blue>bright red color. Why?
What is the treatment for raynaud phenomenon?
Warm the hands
Why do obese pts present with osteoarthritis?
The knee suffers a concentration of pressure per unit area higher than any other weight bearing joint. The continually increased pressure on the cartilage causes pressure atrophy, progressing to injury and necrosis.
List 5 possible mechanisms by which obesity leads to cancer.
1) Excess estrogen produced by fat
2) Increased insulin & I-LGF
3) Excess leptin promotes cell proliferation
4) Fat cell may have direct and indirect effects on other tumor growth factors including mTOR adn AMP-activated protein kinase.
5) Chronic low-level inflammation
What hormone, secreted by the ilium and colon, is implicated in reducing desire to eat?
Amylin, a hormone released from B-cells in the pancreas alongside insulin, has what effect on food intake and weight gain?
Reduces food intake and reduces weight gain
T/F: total # of adipocytes is established in adulthood.
False, childhood and adolescence. That's why childhood obesity is such a concern to health in later life.
T/F: the total # of adipocytes fluctuates throughout life.
False. # of cells doesn't change, just size of individual cells. # is established in childhood.
Why is maintaining weight losses from dieting so difficult?
The body's natural homeostasis try to keep body fat constant over time. Unless diet an exercise are sustained, the body returns to pre-diet levels.
Does simply adding "good" fatty acids like Omega-3 to one's diet improve CV health?
No, but substituting good for bad does.