Path Book: Chapter 7 Environmental and Nutritional Diseases pg. 287-306

Question 1

Injury induced by physical agents is divided into the following categories:

Answer 1

1) mechanical trauma,
2) thermal injury,
3) electrical injury, and
4) injury produced by ionizing radiation.

Question 2

What are some kinds of mechanical trauma?

Answer 2

All soft tissues react similarly to mechanical forces, and the patterns of injury can be divided into abrasions, contusions, lacerations, incised wounds, and punc- ture wounds

Question 3

What is an abrasion?

Answer 3

a wound produced by scraping or rubbing the skin surface, damaging the superficial layer. Typical skin abrasions remove only the epidermal layer

Question 4

What is a contusion?

Answer 4

or bruise, is a wound usually produced by a blunt trauma and is characterized by damage to vessel and extravasation of blood into tissues.

Question 5

What is a laceration?

Answer 5

A laceration is a tear or disruptive stretching of tissue caused by the application of force by a blunt object. In contrast with an incision, most lacerations have intact bridging blood vessels and jagged, irregular edges*

Question 6

What is an incised wound?

Answer 6

one inflicted by a sharp instrument. The bridging blood vessels are severed.

Question 7

What is a puncture wound? A penetrating one?

Answer 7

A puncture wound is typically caused by a long, narrow instrument and is termed penetrating when the instrument pierces the tissue and perforating when it traverses a tissue to also create an exit wound.

Question 8

How can a forensic pathologist tell the distance of gun shot?

Answer 8

Gunshot wounds are special forms of puncture wounds that demonstrate distinctive features important to the forensic pathologist. A wound from a bullet fired at close range leaves powder burns, whereas one fired from more than 4 or 5 feet away does not

Question 9

The clinical severity of burns depends on what important variables?

Answer 9

1) Depth
2) Percentage of body surface involved
3) Whether internal injuries from inhalation of hot or toxic fumes are present
4) Promptness and efficacy of therapy, especially fluid and electrolyte management and prevention or control of wound infections

Question 10

What is a full-thickness burn?

Answer 10

A full-thickness burn produces total destruction of the epidermis and dermis, including the dermal appendages that harbor cells needed for epithelial regeneration. Both third- and fourth-degree burns are in this category.

Question 11

What are partial-thickness burns?

Answer 11

In partial-thickness burns, at least the deeper portions of the dermal appendages are spared. Partial-thickness burns include first-degree burns (epithelial involvement only) and second-degree burns (involving both epidermis and superficial dermis).

Question 12

Despite continuous improvement in therapy, any burn exceeding ___ of the total body surface, whether superficial or deep, is grave and potentially fatal.

Answer 12

50%

Question 13

What happens in burns that cover over 20% of the body’s surfaces?

Answer 13

With burns of more than 20% of the body surface, there is a rapid shift of body fluids into the interstitial compartments, both at the burn site and systemically, which can result in hypovolemic shock

Question 14

Is the edematous exudate associated with extensive burns transudate like or exudate like?

Answer 14

More exudate. Because protein from the blood is lost into interstitial tissue, generalized edema, including pulmonary edema, may become severe.

Question 15

What is the leading cause of death in burn patients?

Answer 15

Organ system failure resulting from sepsis

Question 16

Why are burn sites so hospitable for infection?

Answer 16

The burn site is ideal for growth of microorganisms; the serum and debris provide nutrients, and the burn injury compromises blood flow, blocking effective inflammatory responses.

Furthermore, cellular and humoral defenses against infections are compromised, and both lymphocyte and phagocyte functions are impaired. Direct bacteremic spread and release of toxic sub- stances such as endotoxin from the local site have dire consequences

Question 17

What is the most common infection in burn patients?

Answer 17

The most common offender is the opportunist Pseudomonas aeruginosa, but antibiotic-resistant strains of other common hospital-acquired bacteria, such as S. aureus, and fungi, particularly Candida spp., also may be involved.

Question 18

What else is common in burn states?

Answer 18

development of a hypermetabolic state, with excess heat loss and an increased need for nutritional support. It is estimated that when more than 40% of the body surface is burned, the resting metabolic rate may approach twice normal.

Question 19

What is heat exhaustion caused by?

Answer 19

Its onset is sudden, with prostration and collapse, and it results from a failure of the cardio- vascular system to compensate for hypovolemia, sec- ondary to water depletion. After a period of collapse, which is usually brief, equilibrium is spontaneously reestablished.

Question 20

What is heat stroke caused by?

Answer 20

associated with high ambient temperatures and high humidity. Thermoregulatory mechanisms fail, sweating ceases, and core body temperature rises.

Question 21

What is the underlying basis of heat stroke?

Answer 21

The underlying mechanism is marked generalized peripheral vasodilation with peripheral pooling of blood and a decreased effective circulating blood volume. Necrosis of the muscles and myocardium may occur. Arrhythmias, disseminated intravascular coagulation, and other systemic effects are common.

Question 22

What is Malignant hyperthermia caused by?

Answer 22

It is a genetic condition resulting from mutations in genes such as RYR1 that control calcium levels in skeletal muscle cells. In affected individuals, exposure to certain anesthetics during surgery may trigger a rapid rise in calcium levels in skeletal muscle, which in turn leads to muscle rigidity and increased heat production. The resulting hyperthermia has a mortality rate of approxi- mately 80% if untreated, but this falls to less than 5% if the condition is recognized and muscle relaxants are given promptly.

Question 23

Why can’t you let go of a live wire if it is alternating current?

Answer 23

It induces tetanic muscle spasm, so that when a live wire or switch is grasped, irreversible clutching is likely to occur, prolonging the period of current flow.

Question 24

What is the difference between ionizing and non ionizing radiation?

Answer 24

Only ionizing radiation has sufficient energy to remove tightly bound electrons.

Question 25

In addition to the physical properties of the radiation, its biologic effects depend heavily on the following variables:

Answer 25

1) Rate of delivery
2) Field size
3) Cell proliferation
4) Hypoxia
5) Vascular damage

Question 26

Why does rate of delivery impact radiation effect?

Answer 26

Although the effect of radiant energy is cumulative, delivery in divided doses may allow cells to repair some of the damage in the intervals. Thus, fractional doses of radiant energy have a cumulative effect only to the extent that repair during the intervals is incomplete. Radiotherapy of tumors exploits the capability of normal cells to repair themselves and recover more rapidly than tumor cells.

Question 27

Why does field size impact radiation effect?

Answer 27

The size of the field exposed to radiation has a great influence on its consequences. The body can sustain relatively high doses of radiation when they are delivered to small, carefully shielded fields, whereas smaller doses delivered to larger fields may be lethal.

Question 28

Why does cell proliferation radiation effect?

Answer 28

Because ionizing radiation damages DNA, rapidly dividing cells are more vulnerable to injury than are quiescent cells. Except at extremely high doses that impair DNA transcription, DNA damage is compatible with survival in nondividing cells, such as neurons and muscle cells. However, in dividing cells, chromosome abnormalities and other types of muta- tions are recognized by cell cycle checkpoint mecha- nisms, which lead to growth arrest and apoptosis.

Understandably, therefore, tissues with a high rate of cell turnover, such as gonads, bone marrow, lymphoid tissue, and the mucosa of the GI tract, are extremely vulnerable to radiation, and the injury is manifested early after exposure.

Question 29

Why does hypoxia impact radiation effect?

Answer 29

The production of reactive oxygen species by the radiolysis of water is the most important mechanism of DNA damage by ionizing radiation. Tissue hypoxia, such as may exist in the center of rapidly growing poorly vascularized tumors, may thus reduce the extent of damage and the effectiveness of radiotherapy directed against tumors.

Question 30

Why does vascular damage impact radiation effect?

Answer 30

Damage to endothelial cells, which are moderately sensitive to radiation, may cause narrowing or occlusion of blood vessels, leading to impaired healing, fibrosis, and chronic ischemic atrophy. These changes may appear months or years after exposure. Despite the low sensitivity of brain cells to radiation, vascular damage after irradiation can lead to late manifestations of radiation injury in this tissue.

Question 31

How can ionizing radiation damage DNA?

Answer 31

Ionizing radiation can cause many types of damage in DNA, including base damage, single- and double-strand breaks, and cross-links between DNA and protein

failure to repair can lead to tumor formation

Question 32

A common consequence of cancer radiotherapy is the development of ___ in the irradiated field.

Answer 32

fibrosis. Fibrosis may occur weeks or months after irradiation, leading to the replacement of dead parenchymal cells by connective tissue and the formation of scars and adhesions.

Question 33

What are the most sensitive organs to ionizing radiation?

Answer 33

gonads, the hematopoietic and lymphoid systems, and the lining of the GI tract.

Question 34

How are the hematopoietic and lymphoid systems affected by ionizing radiation?

Answer 34

With high dose levels and large exposure fields, severe lymphopenia may appear within hours of irradiation, along with shrinkage of the lymph nodes and spleen. Radiation directly destroys lymphocytes, both in the circulating blood and in tissues (nodes, spleen, thymus, gut). With sublethal doses of radiation, regeneration from viable progenitors is prompt, leading to restoration of a normal lymphocyte count in the blood within weeks to months. The circulating granulocyte count may first rise but begins to fall toward the end of the first week. Levels near zero may be reached during the second week. If the patient survives, recovery of the normal granulocyte count may require 2 to 3 months. Platelets are affected as well, with the nadir of the count occurring somewhat later than that for granulocytes; recovery is similarly delayed. Hematopoietic cells in the bone marrow, including red cell precursors, also are quite sensitive to radiant energy. Red cells are radioresistant, but red cell progenitors are not; as a result, anemia appears after 2 to 3 weeks and may persist for months.

Question 35

T or F. Any cell capable of division that has sustained mutations has the potential to become cancerous.

Answer 35

T. Thus, an increased incidence of neoplasms may occur in any organ after exposure to ionizing radiation

Exposure of large areas of the body to even very small doses of radiation may have devastating effects.

Question 36

What is the difference between primary and secondary malnutrition?

Answer 36

In primary malnutrition, one or all of the required sources of nutrition (carbs, proteins, etc.) are missing from the diet. By contrast, in secondary, or conditional, malnutrition, the dietary intake of nutrients is adequate, and malnutrition results from nutrient malabsorption, impaired utilization or storage, excess losses, or increased requirements (pregnancy).

Question 37

The causes of secondary malnutrition can be grouped into three general but over- lapping categories:

Answer 37

GI diseases, chronic wasting diseases, and acute critical illness.

Question 38

What conditions might cause an increased nutritional need?

Answer 38

The basal metabolic rate becomes accelerated in many illnesses (in patients with extensive burns, it may double), pregnancy, infancy

Question 39

What is PEM?

Answer 39

protein-energy malnutrition

Question 40

What are the two main protein compartments in the body?

Answer 40

1) the somatic compartment, represented by proteins in skeletal muscles, and
2) the visceral compartment, represented by protein stores in the visceral organs, primarily the liver.

These two compartments are regulated differently

Question 41

The somatic compartment is depleted in ___, while the visceral compartment is depleted in ____.

Answer 41

marasmus; kwashiokor

Question 42

How would you measure adequacy of the visceral and somatic protein compartments?

Answer 42

visceral- serum proteins such as albumin and transferrin

somatic- muscle mass

Question 43

What is marasmus? Symptoms?

Answer 43

A child is considered to have marasmus when weight level falls to 60% of normal for sex, height, and age. A marasmic child suffers growth retardation and loss of muscle mass as a result of catabolism and depletion of the somatic protein compartment. Skeletal muscle affected.

Anemia and manifestations of multivitamin deficiencies are present, and there is evidence of immune deficiency, particularly of T cell– mediated immunity.

Question 44

Which is typically depleted first, the somatic or the visceral compartment?

Answer 44

Somatic. The visceral protein compartment, which presumably is more precious and critical for survival, is depleted only marginally (so serum albumin levels are either normal or only slightly reduced in marasmus)

Question 45

What is kwashiorkor? Symptoms?

Answer 45

Kwashiorkor occurs when protein deprivation is relatively greater than the reduction in total calories.

In kwashiorkor, unlike in marasmus, marked protein deprivation is associated with severe loss of the visceral protein compartment, and the resultant hypoalbuminemia gives rise to generalized or dependent edema

In further contrast with marasmus, there is relative sparing of subcutaneous fat and muscle mass. The modest loss of these compartments may also be masked by edema.

Question 46

What else do kwashiorkor patients have?

Answer 46

characteristic skin lesions with alternating zones of hyperpigmentation, des- quamation, and hypopigmentation, giving a “flaky paint” appearance

liver enlargement, small bowel loses crypts, lactate intolerance

As in marasmus, vitamin deficiencies are likely to be present, as are defects in immunity and secondary infections.

Question 47

What is a very common symptom of anorexia nervosa?

Answer 47

Amenorrhea, resulting from decreased secretion of gonadotropin-releasing hormone (and consequent decreased secretion of luteinizing and follicle-stimulating hormones), is so common that its presence is almost a diagnostic feature

Question 48

Other symptoms of anorexia nervosa?

Answer 48

Other common findings, related to decreased thyroid hormone release, include cold intolerance, bradycardia, constipation, and changes in the skin and hair. In addition, dehydration and electrolyte abnormalities are frequent findings. The skin becomes dry and scaly and may be yellow-tinged as a result of excess carotene in the blood. Body hair may be increased but usually is fine and pale (lanugo). Bone density is decreased, most likely because of low estrogen levels, which mimics the postmenopausal acceleration of osteoporosis. As expected with severe PEM, anemia, lymphopenia, and hypoalbuminemia may be present.

A major complication of anorexia nervosa is an increased susceptibility to cardiac arrhythmia and sudden death, both due to hypokalemia.

Question 49

Is amenorrhea common in bulimia?

Answer 49

Although menstrual irreg- ularities are common, amenorrhea occurs in less than 50% of bulimic patients, probably because weight and gonado- tropin levels are maintained near normal.

Question 50

Symptoms of bulimia?

Answer 50

The major medical complications are related to continual induced vomiting and chronic use of laxatives and diuretics. These include:

(1) electrolyte imbalances (hypokalemia), which predispose the patient to cardiac arrhythmias;
(2) pulmonary aspiration of gastric contents; and
(3) esophageal and stomach rupture.

Nevertheless, there are no specific signs and symptoms for this syndrome, and the diagnosis must rely on a comprehensive psychologic assessment of the patient.

Question 51

Which vitamins are fat-soluble?

Answer 51

A,D,E, and K. The remainder are water- soluble.

Question 52

Which vitamins can be synthesized endogenously?

Answer 52

vitamin D from precursor steroids, vitamin K and biotin by the intestinal microflora, and niacin from tryptophan, an essential amino acid.

Question 53

What are some important sources of pre-formed vitamin A? Other sources?

Answer 53

Animal-derived foods such as liver, fish, eggs, milk, and butter

Yellow and leafy green vegetables such as carrots, squash, and spinach supply large amounts of carotenoids (β-carotene), many of which are provitamins that are metabolized to active vitamin A in the body.

Question 54

T or F. As with all fats, the digestion and absorption of carotenes and retinoids (aka vitamin A) require bile and pancreatic enzymes.

Answer 54

T.

Question 55

Where is most of the vitamin A in the body stored?

Answer 55

More than 90% of the body’s vitamin A reserves are stored in the liver, pre- dominantly in the perisinusoidal stellate (Ito) cells.

In healthy persons who consume an adequate diet, these reserves are sufficient to support the body’s needs for at least 6 months.

Question 56

In humans, the best-defined functions of vitamin A are the following:

Answer 56

• Maintaining normal vision in reduced light
• Potentiating the differentiation of specialized epithelial
cells, mainly mucus-secreting cells
• Enhancing immunity to infections, particularly in children with measles

Question 57

How is vitamin A cycled through the body from the liver?

Answer 57

Retinol esters stored in the liver can be mobilized; before release, retinol binds to a specific retinol- binding protein (RBP), synthesized in the liver. The uptake of retinol and RBP in peripheral tissues is dependent on cell surface RBP receptors. After uptake by cells, retinol is released, and the RBP is recycled back into the blood. Retinol may be stored in peripheral tissues as retinyl ester or be oxidized to form retinoic acid

Question 58

What vitamin A compounds are involved in light processing?

Answer 58

It involves four forms of vitamin A-containign pigments: rhodopsin, located in rod cells, and three iodopsins, each responsive to a specific color in bright light.

Question 59

How is rhodopsin synthesized from retinol?

Answer 59

The synthesis of rhodopsin from retinol involves:

(1) oxidation to all-trans-retinal, (2) isomerization to 11-cis-retinal, and (caused by light)
(3) interaction with opsin to form rhodopsin.

During dark adaptation, some of the all-trans- retinal is reconverted to 11-cis-retinal, but most is reduced to retinol and lost to the retina, explaining the need for continuous supply of retinol.

Question 60

What are some causes of vitamin A deficiency besides simply not getting enough?

Answer 60

In children, stores of vitamin A are depleted by infections, and the absorption of the vitamin is poor in newborn infants. In adults, vitamin A deficiency, in conjunction with depletion of other fat-soluble vitamins, may develop in conjunction with malabsorption syndromes, such as celiac disease, Crohn disease, and colitis. Bariatric surgery and continuous use of mineral oil laxatives also may lead to deficiency.

Question 61

One of the earliest manifestations of vitamin A deficiency is ____.

Answer 61

impaired vision, particularly in reduced light (night blindness).

Question 62

How can vitamin A deficiency cause complete blindness?

Answer 62

Persistent deficiency gives rise to a series of changes involving epithelial metaplasia and keratization. The most devastating changes occur in the eyes and result in the clinical entity referred to as xerophthalmia (dry eye). First, there is dryness of the conjunctiva (xerosis conjunctivae) as the normal lachrymal and mucus-secreting epithelium is replaced by keratinized epithelium. This is followed by a buildup of keratin debris in small opaque plaques (Bitot spots) in the sclera and, eventually, the erosion of the roughened corneal surface, leading to softening and destruction of the cornea (keratomalacia) and total blindness.

Question 63

What are some sources of vitamin A toxicity?

Answer 63

the livers of whales, sharks, and even tuna

Question 64

What is the main role of Vitamin D in the body?

Answer 64

The major function of the fat-soluble vitamin D is the maintenance of normal plasma levels of calcium and phosphorus.

Question 65

What is the major source of vitamin D in humans?

Answer 65

endogenous synthesis in the skin by photochemical conversion of a precursor, 7-dehydrocholesterol, powered by light energy. Irradiation of this compound forms cholecalciferol, known as vitamin D3

Question 66

Describe the metabolism of vitamin D.

Answer 66

1. Absorption of vitamin D along with other fats in the gut or synthesis from precursors in the skin
2. Binding to plasma α1-globulin (vitamin D–binding protein) and transport to liver
3. Conversion to 25-hydroxyvitamin D (25-OH-D) by 25-hydroxylase in the liver
4. Conversion of 25-OH-D to 1,25-dihydroxyvitamin D [1,25-(OH)2-D] (biologically the most active form of vitamin D) by α1-hydroxylase in the kidney

Question 67

Renal production of 1,25-(OH)2-D is regulated by what three mechanisms?

Answer 67

• Hypocalcemia stimulates secretion of parathyroid hormone (PTH), which in turn augments the conversion of 25-OH-D to 1,25-(OH)2-D by activating α1-hydroxylase.
• Hypophosphatemia directly activates α1-hydroxylase, thereby increasing the formation of 1,25(OH)2-D.
• In a feedback loop, increased levels of 1,25-(OH)2-D downregulate the synthesis of this metabolite by inhibiting the action of α1-hydroxylase (decreases in 1,25- (OH)2-D have the opposite effect).

Question 68

How does vitamin D perform its effector functions?

Answer 68

Like retinoids and steroid hormones, 1,25- (OH)2-D acts by binding to a high-affinity nuclear receptor that in turn binds to regulatory DNA sequences, thereby inducing transcription of specific target genes. The receptors for 1,25-(OH)2-D are present in most nucleated cells of the body, and they transduce signals that result in various biologic activities, beyond those involved in calcium and phosphorus homeostasis.

Question 69

What are some of the functions of the activated form of vitamin D?

Answer 69

• Stimulates intestinal absorption of calcium through upregulation of calcium transport, in enterocytes
• Stimulates calcium resorption in renal distal tubules.
• Collaborates with PTH to regulate blood calcium. This occurs in part through upregulation of RANK ligand on osteoblasts, which in turn activates RANK receptors on osteoclast precursors. RANK activation produces signals that increase osteoclast differentiation and bone resorptive activities.
• Promotes the mineralization of bone. Vitamin D is needed for the mineralization of osteoid matrix and epiphyseal cartilage during the formation of flat and long bones. It stimulates osteoblasts to synthesize the calcium- binding protein osteocalcin, which promotes calcium deposition.

Question 70

Effects of vitamin D on bone depend on what?

Answer 70

plasma levels of calcium: On the one hand, in hypocalcemic states 1,25-(OH)2-D together with PTH increases the resorption of calcium and phosphorus from bone to support blood levels. On the other hand, in normocalcemic states vitamin D also is required for calcium deposition in epiphyseal cartilage and osteoid matrix.

Question 71

What are the main diseases of vitamin D deficiency?

Answer 71

Rickets in growing children and osteomalacia in adults- the basic derangement is an excess of unmineralized bone matrix.

They may result from diets deficient in calcium and vitamin D, but probably more important is limited exposure to sunlight

Whatever the basis, a deficiency of vitamin D tends to cause hypocalcemia.

Question 72

A deficiency of water-soluble vitamin C (absorb acid) leads to the development of ____.

Answer 72

scurvy, characterized principally by bone disease in growing children and by hemorrhages and healing defects in both children and adults.

easily bruised, corkscrew hair (bleeding around hair follicles), dry skin, Periungual hemorrhage (small bleeding under nails), hair and tooth loss

Question 73

Is vitamin C made in the body?

Answer 73

Unlike vitamin D, ascorbic acid is not synthesized endogenously in humans, who therefore are entirely dependent on the diet for this nutrient. Vitamin C is present in milk and some animal products (liver, fish) and is abundant in a variety of fruits and vegetables. All but the most restricted diets provide adequate amounts of vitamin C.

Question 74

What are the main functions of vitamin C in the body?

Answer 74

1) Activation of prolyl and lysyl hydroxylases from inactive precursors, allowing for hydroxylation of pro collagen.
2) ability to scavenge free radicals directly and participation in metabolic reactions that regenerate the antioxidant form of vitamin E.

Question 75

What is a normal BMI range?

Answer 75

The BMI is closely correlated with body fat. BMIs in the range 18.5 to 25 kg/m2 are considered normal, while BMIs between 25 and 30 kg/m2 identify the overweight, and BMIs greater than 30 kg/m2, the obese.

Question 76

T or F. The untoward effects of obesity are related not only to the total body weight but also to the distribution of the stored fat.

Answer 76

Central, or visceral, obesity, in which fat accumulates in the trunk and in the abdominal cavity (in the mesentery and around viscera), is associated with a much higher risk for several diseases than is excess accumulation of fat in a diffuse distribution in subcutaneous tissue.

Question 77

What is leptin and what does it do?

Answer 77

a cytokine released by adipocytes that has a net effect of reducing food intake and enhance the expenditure of energy.

Question 78

In a simplified way the neurohumoral mechanisms that regulate energy balance and body weight may be divided into three components

Answer 78

The peripheral or afferent system generates signals from various sites. Its main components are leptin and adiponectin produced by fat cells, insulin from the pancreas, ghrelin from the stomach, and peptide YY from the ileum and colon. Leptin reduces food intake. Ghrelin secretion stimulates appetite, and it may function as a “meal- initiating” signal. Peptide YY, which is released post- prandially by endocrine cells in the ileum and colon, is a satiety signal.

• The arcuate nucleus in the hypothalamus, which processes and integrates the peripheral signals and generates new signals that are transmitted by (1) POMC (pro-opiomelanocortin) and CART (cocaine- and amphetamine-regulated transcript) neurons; and (2)NPY (neuropeptide Y) and AgRP (agouti-related
peptide) neurons.

• The efferent system, which consists of hypothalamic
neurons regulated by the arcuate nucleus. POMC/ CART neurons activate efferent neurons that enhance energy expenditure and weight loss, while NPY/AgRP neurons activate efferent neurons that promote food intake and weight gain. Signals transmitted by efferent neurons also communicate with forebrain and midbrain centers that control the autonomic nervous system.

Question 79

What is the output of leptin regulated by?

Answer 79

the output of leptin is regulated by the adequacy of fat stores.

Question 80

How does leptin work?

Answer 80

With abundant adipose tissue, leptin secretion is stimulated, and the hormone travels to the hypothalamus, where it reduces food intake by stimulating POMC/CART neurons and inhibiting NPY/AgRP neurons.

Leptin also increases energy expenditure by stimulating physical activity, energy expenditure, and thermogenesis,

In rodents and humans, loss-of-function mutations affecting components of the leptin pathway give rise to massive obesity.

Question 81

Where is gherlin produced and what does it do?

Answer 81

Ghrelin is produced in the stomach and is the only known gut peptide that increases food intake.

It probably acts by stimulating the NPY/AgRP neurons in the hypothalamus

Question 82

What does PYY do?

Answer 82

PYY is secreted from endo- crine cells in the ileum and colon in response to consump- tion of food. It presumably acts by stimulating POMC/ CART neurons in the hypothalamus, thereby decreasing food intake.

Question 83

What is secondary PEM?

Answer 83

common in chronically ill or hospitalized patients. A particularly severe form of secondary PEM, called cachexia, often develops in patients with advanced cancer. The wasting is all too apparent and often presages death. Although loss of appetite may partly explain it, cachexia may appear before appetite decreases.

Question 84

What causes secondary PEM?

Answer 84

The underlying mechanisms are complex, but appear to involve “cachectins” such as proteolysis-inducing factor, which are secreted by tumor cells, and cytokines, particularly TNF, which are released as part of the host response to advanced tumors. Both types of factors directly stimulate the degradation of skeletal muscle proteins, and cytokines such as TNF also stimulate fat mobilization from lipid stores.