Option D. Anthracotic pigment: Alizarin Red

D. The material is triglyceride; the change is reversible.

The Correct Answer is A. The stain is blue; the pigment is hemosiderin

The Correct Answer is A. Prussian blue stain

Hemosiderin

1. A hemoglobin-derived, iron-containing yellow-brown granular pigment
2. About 25% of the body’s total iron content is in an intracellular storage pool composed of ferritin and hemosiderin
3. Hemosiderin is a partially denatured from of ferritin that easily aggregates and is recognized microscopically
1. Iron is normally carried by specific transport glycoproteins, transferrins, in plasma. In cells, it is stored in association with a protein, apoferritin, to form ferritin micelles. Ferritin is present virtually all cells, but is particularly abundant in the liver and bone marrow. When there is a local or systemic excess of iron, ferritin forms hemosiderin granules. In most cases hemosiderin causes no damage to the cell.
4. Hemosiderin is commonly seen in areas of congestion or hemorrhage or where there is excessive breakdown of RBCs
1. Macrophages phagocytize the RBC debris and the lysosomal enzymes eventually convert the hemoglobin, through a sequence of pigments, into hemosiderin.
5. Conditions where you might see hemosiderin
1. Under normal conditions, small amount of hemosiderin can be seen in macrophages of the bone marrow, spleen and liver, all actively engaged in RBC breakdown
2. In animals with congestive heart failure it is commonly found in alveolar macrophages and grossly may impart a yellowish tan to brown color to the lung, referred to as pulmonary hemosiderosis
3. Hemochromatosis – Excessive accumulation of iron in parenchymal organs such as the liver and pancreas, either from a genetic defect causing excessive iron absorption (hereditary hemochromatosis) or as consequence of parenteral administration of iron (secondary hemochromatosis).
4. Heartworm Disease
5. Thromboembolism
6. Pulmonary hemosiderosis secondary to heart failure
7. Cerebral infarct
6. Staining technique
1. Prussian blue reaction, specific for iron
2. H&E stain: section showing golden-brown, finely granular pigment

The Correct Answer is C. Skeletal muscle

The correct answer is C. uterine growth during pregnancy

The correct Answer is b. hyperplasia

The Correct Answer is d. hypertrophy

Systemic (left-sided) hypertensive heart disease (HHD):

• adaptive response to pressure overload

• can lead to myocardial dysfunction, cardiac dilation, CHF, and sudden death

• Dx criteria: LV hypertrophy (concentric) + HT

The correct answer is b acute tubular necrosis

Acute tubular necrosis (ATN)

1. Tubular epithelial cell destruction with acute renal cell suppression
1. Most common cause of renal failure, also caused by
1. Severe glomerular disease (RPGN)
1. Diffuse renal vascular disease (polyarteritis nodosa)
2. Acute papillary necrosis
3. Acute drug induced interstitial nephritis
4. Diffuse cortical necrosis
2. ATN Causes
1. Ischemic ATN Setting of hypotension and shock – ischemic ATN
2. Nephrotoxic ATN:
1. metal (Hg), CCl₄,
2. drugs(gentamicin)
3. contrast agents
3. Pathogenesis
1. Tubular injury (reversible & irreversible)
2. Persistent & severe blood flow disturbance
1. RAS system is involved: positive feedback for vasoconstriction
4. MOST COMMON CAUSE OF RENAL FAILURE
1. Suppression of renal function with urine flow falling below 400ml (oliguria)
5. Tubular injury – LOSS OF CELL POLARITY
1. Redistribution of MEM protein from basolateral to luminal side of tubular cells
1. Increased Na to distal tubules – vasoconstriction
2. Interstitial edema from damaged tubules can increase pressure and cause collapse
2. Disturbance in blood flow – ischemic renal injury causing reduced GFR
1. intrarenal vasoconstriction due to sublethal endothelial injury causing increased
1. endothelin release and
2. decreased nitric oxide
2. direct effect of ischemia or toxins on the glomerulus
3. Tubulorrhexis – rupture of BM
1. Casts in distal tubules and collecting ducts
2. Tamm-Horsfall protein hemoglobin, plasma protein
3. PMN, lymphocytes, PC
4. Toxic ATN – similar with most damage in proximal tubule, BM spared
5. Epithelial regeneration within a week – cuboidal epithelial covering
6. Clinical course
1. Initiating phase ~ 36hrs,
1. ischemia with slight decline in urine output, ↑ BUN
2. Maintenance phase – up to 3 weeks, urine output <400ml
3. Recovery phase
1. ↑urine output (up to 3L/day for a few days), increased infection
2. 25% OF DEATHS IN RECOVERY PHASE
3. gradual return of well-being,
1. urine volume normalizes,
2. subtle functional impairment for months,
• 90-95% survival

The correct answer is E. anthracosis

Anthracosis (coal worker's pneumoconiosis) is a diffuse nodular deposition of dust in the lungs as a result of a long term exposure to bituminous or anthracite coal dust in coal mining. In simple coal workers pneumoconiosis, coal dust is widely distributed throughout the lungs leading to the development of coal “macules“ around the bronchioles. Later on a mild dilatation known as focal dust emphysema also occurs; however it does not extend to the alveoli and is not associated with airflow obstruction. However, each year about 1- 2 % of miners with simple anthracosis go on to develop progressive massive fibrosis, which can sometimes develop after the exposure has ceased, or it may progress without further exposure.

The Correct Answer is B. Pigment from cellular breakdown

Lipochrome (lipofuschin) pigments

These are the breakdown products within cells from oxidation of lipids and lipoproteins. They are the wear-and-tear pigments found most commonly in heart, liver, CNS, and adrenal cortex (zona reticularis). The less highly oxidized "ceroid" pigment of testis interstitium and seminal vesicle is another form of lipochrome.Lipochrome can be stained by Sudan black B, long Ziehl-Neelson acid fast, and Schmorl's methods. Lipochrome may also exhibit a strong orange auto fluorescence in formalin-fixed, unstained paraffin sections.

Answer D

Action potentials are not required for contractions in the stomach, but are required for contractions in the small intestine.

Answer C

Medium chain fatty acids (C<16) are water-soluble enough to directly enter the bloodstream from the enterocytes without having to be reesterified and formed into chylomicrons or VLDLs. Chylomicrons are too large to go directly into the bloodstream but have to enter capillaries via the thoracic duct of the lymphatic system.

Answer D

Mass movement is responsible for moving colonic contents into the rectum. Segmentation contractions are responsible for mixing the contents of the colon, and peristaltic contractions only move the contents a short distance. The recto-sphincteric reflex occurs when fecal material is in the rectum - the rectum contracts and the internal anal sphincter relaxes. There is no MMC in the large intestine.

Answer B

Answer C

The striated ducts in the salivary glands absorb Na+ and Cl-, making saliva hypotonic to plasma. When flow rate increases, however, there is less time for this absorption to occur. So there are increased concentrations of Na+ and Cl- at higher flow rates. Salivary secretion is under total autonomic nervous system control. It is unusual in that both the parasympathetic and sympathetic systems stimulate secretion, but the stimulation by the sympathetic system is transient. The volume of secretions relative to the mass of the glands is very large.

Answer E

Motility of the small intestine is definitely affected by both the autonomic and enteric nervous systems. The gastroileal and intestinointestinal reflexes depend on the extrinsic nervous systems. Segmentation contractions are the most common type of contractions, which serve to mix the chyme with digestive juices. The frequency of contractions is higher in the proximal intestine than in the distal intestine. This serves to propel the chyme towards the colon. As opposed to the stomach, action/spike potentials are required on top of slow waves in the small intestine for contractions to occur. But like the stomach, there is a migrating motility complex every 90 minutes which clears the remqaining chyme from the small intestine.

Option A


It is during the intestinal phase of pancreatic secretions that you need the enzymes. So CCK, secreted from the I cells in the duodenum in response to fat and protein digestion products, acts on the acinar cells to increase enzyme secretion. CCK also potentiates the response of the ductal cells to secretin. Na+ concentrations are always isotonic with plasma and do not change with flow rate. HCO3- concentrations are always higher than plasma at all flow rates, and it enters the lumen in exchange for Cl-. The rate of bicarbonate secretion is dependent on the amount of Cl- present in the lumen.

Answer: b



Glutamine is the most studied gut-specific nutrient. Glutamine has been classified as a nonessential or nutritionally dispensable amino acid since glutamine can be synthesized in adequate quantities from other amino acids and precursors. Glutamine is not included in most nutritional formulas and has been eliminated from TPN solutions because of its relative instability and short half life compared to other amino acids. With few exceptions, glutamine is present in oral enteral diets but only at relatively low levels characteristic of the concentration in most animal and plant stores (about 7% of total amino acids). Several recent studies, however, have demonstrated that glutamine may be an essential amino acid during critical illness, particularly as it relates to supporting the metabolic requirements of the intestinal mucosa. These studies demonstrate that dietary glutamine is not required during states of health but appears to be beneficial when glutamine depletion is severe and/or when intestinal mucosa is damaged by insults such as chemotherapy or radiation therapy. The addition of glutamine to enteral diet reduces the incidence of gut translocation but these improvements are dependent upon the amount of supplemental glutamine and the type of insult studied. Glutamine-enriched TPN partially attenuates villous atrophy that develops during parenteral nutrition. The use of intravenous glutamine in patients appears to be safe and effective in its ability to maintain muscle glutamine stores and improve nitrogen balance. In contrast to glutamine, short chain fatty acids are primary energy source for colonocytes.

Answer: a, b, c, d



The pattern of physiologic changes elicited in response to surgical stress results from the specific interaction of an individual patient with a stressful stimulus. Several factors specific to the patient may determine the nature of the host response to stress. Body composition is a major determinant of the metabolic responses observed during surgical illness. Post-traumatic nitrogen excretion is directly related to the size of the body protein mass. A strong relationship between protein depletion and postoperative complications has been demonstrated in nonseptic, nonimmunocompromised patients undergoing elective major gastrointestinal surgery. Protein-depleted patients have significantly lower preoperative respiratory muscle strength and vital capacity, increased incidence of postoperative pneumonia, and longer postoperative hospital stay. Impaired wound healing and respiratory, hepatic, and muscle function in protein-depleted patients awaiting surgery has also been reported. Many of the changes in the metabolic responses to surgical illnesses that occur with aging can be attributed to alterations in body composition and to long-standing patterns of physical activity. Fat mass tends to increase with age and muscle mass tends to decrease. Loss of strength that accompanies immobility, starvation and acute surgical illness may have marked functional consequences. Furthermore, the prevalence of cardiovascular and pulmonary diseases increase with age. Thus, the delivery of oxygen to tissues may be impaired in the elderly. Finally, observed differences in metabolic responses of men and women generally reflect differences in body composition. Lean body mass is lower in women than in men; and this difference is thought to account for the net loss of nitrogen after major elective abdominal surgery generally being lower in women than in men.

Answer: b, d



The degree of hypermetabolism is generally related to the severity of injury. Patients with long-bone fractures have a 15–25% increase in metabolic rate, whereas metabolic rates in patients with multiple injuries increases by 50%. These metabolic rates in trauma patients are contrasted with those in postoperative patients, who rarely increase their BMR by more than 10–15% following operation. Studies have shown that uninjured volunteers are able to dispose of exogenous glucose load much more readily than injured patients. Other studies have demonstrated a failure to suppress hepatic glucose production in trauma patients during glucose loading or insulin infusion. Thus, profound insulin resistance occurs in injured patients. Skeletal muscle is the major source of nitrogen that is lost in the urine following extensive injury. Although it is recognized that amino acids are released by muscle in increased quantities following injuries, it has only been recently appreciated that the composition of amino acid reflux does not reflect the composition of muscle protein. The release is skewed towards glutamine and alanine, each of which comprise about one-third of the total amino acids released by skeletal muscle. To support hypermetabolism, stored triglyceride is mobilized at an accelerated rate. Although mobilization and use of free fatty acids are accelerated in injured subjects, if unfed, severely injured patients rapidly deplete their fat and protein stores.

Answer: a, b, d

Patients with gastrointestinal-cutaneous fistulas represent the classical indication for TPN. In such patients, oral intake of food almost invariably results in increased fistula output with associated metabolic disturbances, dehydration, skin breakdown, and death. Several comprehensive reviews have concluded that TPN clearly impacts on the treatment course of the disease in patients with GI fistulas. The following conclusions can be drawn from studies evaluating the use of TPN in patients with enterocutaneous fistula. First, TPN increases spontaneous closure rate of enterocutaneous fistulas but does not markedly decrease the mortality rate in patients with fistulas. Second, if spontaneous closure of the fistula does not occur, patients are better prepared for operative intervention because of the nutritional support they have received. Finally, certain fistulas are associated with a lower rate of spontaneous closure than others and should be treated more aggressively surgically after a defined period of nutritional support (unless closure occurs).

Answer: c, d



As a general rule, the most important factor to consider when making decisions about the use of TPN in patients with cancer is the response of the tumor to antineoplastic therapy. Appropriate guidelines would include the following: Short-term TPN is indicated in severely malnourished patients or in those in whom gastrointestinal or other toxicities preclude adequate enteral intake for seven days or a longer period. TPN is not indicated in well nourished or mildly malnourished patients undergoing therapy or surgery who would be expected to be able to resume adequate nutrition in approximately seven days. Long-term TPN is indicated in patients in whom treatment associated toxicities preclude the use of enteral nutrition and represent the primary impediment to the restoration of performance status. These patients should be expected to be responding to anti-tumor therapy. Long-term TPN is not indicated with rapidly progressive tumor growth which is unresponsive to such therapy.

Answer: a, c



Basal energy requirements are measured with the subject at rest when no external work is being done; the energy is used mainly for transport and synthetic work within cells. A surprisingly small percentage (< 5%) of this energy is spent on cardiac output and the work of breathing in normal subjects. In contrast, the work of breathing in individuals with chronic obstructive lung disease or in patients on a ventilator may account for 15–20% of caloric expenditure. The average resting post-absorptive 70 kg male consumes about 1500 kcal/day. Energy needs increase as severity of illness increases. The expenditure of kcal is only minimally increased after elective surgery. The largest increase in energy expenditure occurs in patients with severe multiple trauma or major thermal injury. The average-sized adult who sustains a major burn rarely may require more than 3500 kcal/day for maintenance.

Answer: b, c



A number of complications of TPN can occur which can be divided into three types: mechanical, metabolic, and infectious.

Answer: a, c

Numerous clinical trials have failed to yield a consensus with regard to the efficacy of TPN in cancer patients. In 1991, a multicenter VA cooperative trial demonstrated that preoperative TPN is of benefit in surgical patients (many of whom had cancer) with severe preoperative malnutrition. Another study examined the use of routine postoperative TPN following major pancreatic resection. Patients randomized to receive TPN starting on postoperative day 1 were noted to have an increased incidence of intra-abdominal abscesses as well as a tendency towards increased incidence in peritonitis and bowel obstruction. These investigators concluded that routine use of postoperative TPN was not indicated and may, in fact, be harmful following pancreatic resection. In another study, however, perioperative (starting 7 days prior to the planned procedure) TPN for patients undergoing hepatectomy for hepatocellular carcinoma demonstrated that this regimen statistically reduced infectious complications compared to patients who did not receive TPN. This was one of the few studies that demonstrated that routine TPN (without the requirement of severe preoperative malnutrition) was of benefit. The use of TPN in patients receiving bone marrow transplantation has also been shown to be a valuable component of overall care.

Answer: a, c



One of the earliest consequence of a surgical procedure is the rise in levels of circulating cortisol that occur in response to a sudden outpouring of ACTH from the anterior pituitary. The rise in ACTH stimulates the adrenal cortex to elaborate cortisol which remains elevated for 24–48 hours after operation. The neuroendocrine responses to operation also modify the various mechanisms that regulate salt and water excretion. Alterations in serum osmolarity and tonicity of body fluids secondary to anesthesia and operative stress, stimulate the secretion of aldosterone and ADH. Thus, the ability to excrete a water load after elective surgical procedures is restricted, and weight gain secondary to salt and water retention is usual following an operation. Alterations occur in response to the endocrine pancreas following elective operation. Insulin elaboration is diminished and glucagon concentrations rise. The rise in glucagon and the corresponding fall in insulin are important signals to accelerate hepatic glucose production, and, with other hormones (epinephrine and glucocorticoids), gluconeogenesis is maintained.

Answer: a



Most patients undergoing elective operations are adequately nourished. Unless the patient has suffered significant preoperative malnutrition, characterized by weight loss greater than 10–15%, or has major intraoperative or postoperative complications, solutions containing 5% dextrose may be administered for five to seven days before initiation of enteral nutrition, with no detrimental effect on outcome. The usual postoperative surgical patient is given intravenous glucose at 125 cc/hour receives about 500 kcal/day, far less than the actual number of kcal needed to meet energy requirements. The increased cost of feedings and potential complications associated with intravenous nutrition cannot be justified. Although the use of jejunal feedings in the postoperative period may be useful in some patients, especially those undergoing extensive gastrointestinal surgery, this technique would not appear indicated in the patient described above.

Answer: a, d



Cytokines, which are produced at the site of injury by endothelial cells and by diverse immune cells throughout the body, also occupy a pivotal position in the stress response. Cytokines differ from classic endocrine hormones in that they are produced by a variety of cell types and in that they have the capacity to exert their tissue effects locally via direct cell-to-cell communications in a paracrine and/or autocrine fashion. Cytokines can stimulate the production of other cytokines, leading to important cascades which both amplify and diversify the effects of the proximal cytokine. Occasionally, when in excess, cytokines act as hormones and “spill over” into the systemic circulation and become detectable in the bloodstream.

Answer: a, b, c, d



It takes at least three weeks for collagen to undergo sufficient remodeling and cross linking to attain moderate strength. Since most skin sutures are removed at one to two weeks, the wound has only a small fraction of its eventual strength and may therefore disrupt with even modest stress. Therefore, deep sutures are placed in collagen containing structures to maintain the prolonged tension necessary. Dermis, intestinal submucosa, muscular fascia, tendon, ligament, Scarpa’s fascia, and blood vessel wall represent a partial list of tissues with high collagen content.

Answer: c, d



The initial response to injury and disruption of a blood vessel is bleeding. The hemostatic response to this is clot formation to stop hemorrhage. Platelet plug formation initiates the hemostatic process along with clotting factors activated by collagen and the basement membrane proteins exposed by the injury. Platelets then degranulate, releasing the contents of their alpha granules and dense granules, most notably platelet derived growth factor and transforming growth factor b. These substances initiate chemotaxis and proliferation of inflammatory cells, beginning the inflammatory response that will ultimately heal the wound. Tumor necrosis factor and interleukin-1 also stimulate fibroblast proliferation, however are produced by macrophages.

Answer: b, d



Open wounds, whether they be ulcers or open surgical incisions closing by secondary intention, heal with the same sequence of inflammation, matrix deposition, epithelialization, and scar maturation as in all wounds. The major difference is in the healing incisional wound, the healing process progresses in an orderly temporal sequence. In an open wound, the healing events are spatially separated. In the healing wound, a bed of granulation tissue forms over the exposed subcutaneous tissue. Granulation tissue is composed of new capillaries, proliferating fibroblasts, an immature matrix of collagen, proteoglycans, substrate adhesion molecules, and acute and chronic inflammatory cells. Granulation tissue is the cobblestone pink surface of the healthy new tissue in an open wound. The ability of an open wound to form granulation tissue is governed by the blood supply to the tissue and the relative absence of devitalized tissue and bacteria. Epithelialization is therefore enhanced by limiting bacterial growth which presumably interferes via bacterial and phagocytic cell products such as proteases, collagenases, elastases, and other enzymes.

Answer: a, b, c, d, e

Bone marrow suppression, a common consequence of chemotherapy, is detrimental to wound healing. Quantitative and qualitative lymphocyte and monocyte deficiency impairs cellular proliferation in the inflammatory phase of wound healing. Any chemotherapeutic agent that suppresses the bone marrow will impair healing. Glucocorticoids inhibit wound healing based on their anti-inflammatory and immunosuppressive effects. The anti-inflammatory effect of steroids is, in part, the result of inhibiting arachidonic acid metabolism by impairing macrophage migration, and by altering neutrophil function. Glucocorticoids also inhibit the synthesis of procollagen by fibroblasts, thus delaying wound contraction. Radiation injury leads to arteriolar fibrosis and impaired oxygen delivery. In addition, there is progressive obliteration of blood vessels in the radiated area over time. Radiation also causes intranuclear and cytoplasmic damage to fibroblasts, and this appears to limit their proliferative potential. Diabetes mellitus is often associated with decreased healing of open wounds and increased susceptibility of infection. Many factors contribute to poor healing in diabetic patients and most of them reflect local wound ischemia. However, healing is not impaired in a normally perfused area in a well-controlled diabetic. Peripheral arterial occlusive disease secondary to atherosclerosis can be a primary cause of impaired healing, and may be also a cofactor with other conditions.

Answer: a, b, c, d



Shortly after the initial injury, the wound is full of debris which is cleared over the next several days by recruited and activated phagocytic cells. PMNs begin to arrive immediately, reaching large numbers within 24 hours. The PMNs are followed by macrophages which appear in wounds in significant numbers within two to three days. Macrophages are mononuclear phagocytic cells derived from circulating monocytes or resident tissue macrophages. They complete the process of removing all material not necessary for the ensuing steps of wound healing. Lymphocytes also appear in wounds in small numbers during the inflammatory response. The role of lymphocytes in the wound healing process remains to be clarified, but they are thought to be more related to the chronic inflammatory processes than the initial response to wounding. Platelets are anuclear discoid blood elements derived from bone marrow megakarocytes which play a role in the initial hemostatic process as well as releasing chemotactic factors and factors leading to fibroblast proliferation.

Answer: a, d



There are numerous practical implications for the care of wounds and surgical incisions. Meticulous hemostasis reduces the inflammation of phagocytosis necessary to clear the wound of blood. Atraumatic handling of tissue decreases the load of necrotic or nonviable cells at the wound margin. Deep sutures are best placed only into collagen laden structures that will hold tension, i.e., fascia and dermis. These tissues have a tensile strength to hold sutures under tension. Fat does not contain collagen and will not hold tension. Therefore, fatty tissue should not be sutured as a separate layer. Given that epithelialization of an incision is normally complete within 24–48 hours, there is no reason to protect the incision from water beyond this time period. Allowing the patient to wash or shower one or two days after surgery actually serves useful purpose in debriding the wound.

Answer: b



Epithelialization is more rapid under moist conditions than dry conditions. Without dressings, a superficial wound, or one with minimal devitalized tissue forms a scab or crust, meaning that the blood and serum will coagulate, dry, and form a protective moisture barrier over the open wound. If a wound is kept moist with an occlusive dressing, then epithelial migration is optimized. In addition, the pain of an open wound is dramatically reduced under an occlusive dressing. The traditional wet-to-dry dressing if truly left to dry, simply produces desiccation and necrosis of the surface layer of the wound which delays epithelialization. Although wet-to-dry dressings can be effective for debridement of wound exudate, they are generally less desirable than a moist healing environment combined with effective cleaning of the wound (i.e. water irrigation). Any open wound will leak plasma. With more inflammation, the plasma capillary permeability is further increased. This exudate of serum proteins and inflammatory cells serves as a rich culture medium. This, in turn, will continue to cycle bacterial proliferation and lead to further exudate formation. The net result of this cycle is delayed or absent wound healing. In addition, the edema that results from capillary dysfunction, increases the distance for diffusion from oxygen and nutrient sources to their metabolic targets.

Answer: b

Although there are numerous dressing products commercially available at present, no treatment has been demonstrated to improve healing beyond that of standard treatment which adheres to basic principles. In the absence of large amounts of necrotic tissue, wound debridement does not need to be accomplished surgically. Simple water irrigation either with whirlpool or by water from a hand held shower spray can generate enough power to effectively debride most wounds. Frequent moist dressing changes can accomplish this as well, and in some cases, occlusive absorptive dressings can generate enough tissue proteases to effectively degrade proteins which the absorptive dressings remove. Deeper portions of a wound may accumulate exudate and bacteria. In such cases, water irrigation may be particularly useful. Commonly used agents such as hydrogen peroxide actually may be harmful to normal tissue and are weak oxidants and do a poor job of debriding. Enzymatic debriding agents can be effective when used properly. Most of the newer dressing products have been designed to be more absorptive and achieve moist healing without infection from excess exudate. However, it must be emphasized that as long as moist healing is achieved, there has been no evidence that one product is better than another.

Answer: b, c



The proliferative phase of wound healing begins with the formation of a provisional matrix of fibrin and fibronectin as part of the initial clot formation. Initially, the provisional matrix is populated by macrophages; however, by day three fibroblasts appear in the fibronectin-fibrin framework and initiate collagen synthesis. Fibroblasts proliferate in response to growth factors become the dominant cell type during this phase. Growth factors produced by macrophages simultaneously induce angiogenesis which results in the ingrowth and proliferation of endothelial cells, forming new capillaries. This neovascularity is visible through the epithelium and gives the wound a pink or purple-red appearance.

Collagen is the dominant structural molecule in the wound matrix and in the final scar. Collagen is synthesized into an organized cable-like network in a multi-step process with both intra- and intercellular components. The collagen molecule has quantities of two unique amino acids, hydroxyproline and hydroxylysine. The hydroxylization processes which form these amino acids require ascorbic acid (vitamin C) and is necessary for the subsequent stabilization and cross linkage of collagen. The principal collagen type scar is type 1, with lesser amounts of type 3 collagen also present.

Answer: a, d

Within three or four days after injury, macrophages become the dominant cell type in the inflammatory phase of wound healing. The role of macrophages is not limited only to phagocytosis. In addition, macrophages are the source of more than 30 different growth factors and cytokines. These growth factors induce fibroblast proliferation, endothelial cell proliferation (angiogenesis), extracellular matrix production, and recruit and activate additional macrophages. The result is the induction of a wound healing amplification cycle as growth factors recruit macrophages and elicit additional growth factor release. Experimental studies in which antibodies, which either destroy PMNs or block certain aspects of their function, have shown that wounds heal normally, but that healing is significantly impaired without functional macrophages. These studies confirm the dominant role of the macrophage and the inflammatory phase of wound healing.

Answer: c



The role of antibiotics in wound care is controversial. All open wounds are colonized with bacteria. Only when surrounding tissue is invaded (cellulitis) are systemic antibiotics clearly indicated. Antibiotics may also be useful in other situations such as when granulation tissue has a high bacterial count (> 105 organisms/gram tissue), or in the case of reduced resistance to bacteria such as in a diabetic foot ulcer. The routine use of systemic antibiotics for chronic wounds should be avoided to reduce the development of resistant bacterial strains within the wound. Topical ointments are frequently used and can be useful. The topical vehicle may help keep the wound moist and the bacterial count in the wound may be lowered as the result. However, as with most antibiotics, resistant organisms quickly emerge. Silver sulfadiazine, frequently used for burn care, is also useful for chronic wounds. Its broad spectrum of activity, lack of relevant drug-resistant plasmids in bacteria, and its low cost make it a good choice.

Answer: b, c, d



Wound contraction is an important event which contrasts healing open wounds and closed incisions. When open wounds contract, the surrounding skin is pulled over the open wound to reduce its size. This can occur much faster than epithelialization. As opposed to other animals, human skin does not have a significant degree of mobility in most sites and specifically on the lower leg, the skin is tightly adherent and less elastic. Therefore, although contraction may account for 90% of reduction of wound size on the perineum, it accounts for, at most, 30–40% of healing of a lower leg ulcer.

All healing wounds generate a strong contractile force. When this force is exerted across a joint, it may result in scar contracture which may limit the functional range of motion. At the cellular level, the force which drives wound contraction comes from fibroblasts. Fibroblasts, like muscle cells, contain actin microfilaments. When these filaments increase in number, the cells take a morphologic appearance of myofibroblasts. Myofibroblasts are seen in an increased number in contracting wounds and are felt to play an active role in the process of wound contraction.

Answer: a, d



Although the simplest dressing of gauze and tape combined with the use of antibacterial ointment can achieve moist wound healing in most patients. A multitude of other products are available. These can be classified into films, foams, hydrocolloids, hydrogels, and absorptive powders.

Films are semipermeable to water, generally made of polyurethane, and are nonabsorptive. They are useful to achieve a moist wound healing environment over a minimally exudative wound such as split thickness skin graft donor sites.

The hydrocolloids deserve special mention because they have achieved widespread use. These agents contain hydrophilic materials such as karaya or carboxymethyl cellulose with an adhesive material and are covered by a semipermeable polyurethane film. The material adheres to the skin surrounding the wound, is highly absorptive, and achieves a moist healing environment.

Impregnants are generally fine mesh gauze impregnated with either moisturizing, antibacterial, or bactericidal compounds. They are generally not adherent and require a secondary dressing. They do promote reepithelialization and have a antiinfective effect when combined with antibacterial or bactericidal agents.

A variety of absorptive powders and pastes are available which consist of starch copolymers or colloidal hydrophilic particles. These agents have high absorbency for tissue wound fluid and debride necrotic and fibrous material from the wound.

Answer: A

RRR= 24% - 4% = 82% ARR = 24% - 4% = 20%

Option E

This patient has diversion colitis which developed after the diverting colostomy. Symptoms typically develop within 3-36 months after the diverting procedure and include rectal bleeding, tenesmus, anorectal pain, and crampy lower abdominal discomfort. The differential diagnosis is generally between diversion colitis and IBD, although in this patient the possibility of radiation proctitis is raised by the history of radiation for prostate cancer 6 years prior. However, the endoscopic findings are more consistent with a diagnosis of diversion colitis (absence of telangiectasia, etc.). The first three treatment options represent endoscopic therapies for radiation proctitis. Although medical therapy such as cort enemas, 5-ASA enemas, and short-chain fatty acid enemas have been used with some success in diversion colitis, the treatment of choice is surgical reanastomosis and the symptoms should resolve within a few weeks after surgery

Answer A

Immune globulin is recommended for post-exposure prophylaxis for close contacts (as in a dormitory room or household) since fecal-oral spread is most likely in this setting. HAV vaccine's value in post-exposure prophylaxis is unsettled.

Answer D

All patients recover without intervention and no intervention has been subjected to controlled clinical trials.

Answer D

Relapsing hepatitis A. The temporal relationship, the clinical and laboratory features are entirely consistent with this self-limited entity.

Option C

Answer D

Kava-induced hepatotoxicity is based on the exposure history and the clinical features; acute exacerbations of chronic hepatitis B do occur but acute liver failure must be an exceedingly uncommon feature and the absence of evidence of active HBV replication excluded this as a cause; the biochemical picture is inconsistent with alcoholic hepatitis.

Answer B

H. pylori infection may protect against the development of reflux disease because pangastritis leads to a reduction is acid secretory capability. Treatment may lead to recovery of acid secretion and the potential for worsening reflux although eradication studies have not been performed in this population specifically. Therapy for H. pylori is unlikely to alter the natural history of gastric adenocarcinoma and its relationship to cardiac cancer (as opposed to distal antral cancer) is less established. The autoimmune polyglandular Syndrome is associated with atrophic gastritis and pernicious anemia as a consequence of autoimmune destruction of parietal cells (often with positive autoimmune markers) and not from chronic H. pylori infection. Undifferentiated dyspepsia in young patients without trigger factors is appropriately treated with antibiotics in order to cure those with peptic ulcers (1 in 7) and reduce the burden of endoscopy.

Answer E

Even with “ideal” endoscopic and pharmacologic therapy, the risk for rebleeding in this patient within the first 48 hours is about 5%. Endoscopy is required to both confirm the location of the re-bleeding in case therapeutic intervention fails for the second time but also to potentially control the bleeding thereby avoiding the need for surgical or angiographic intervention. Barium studies are contraindicated in this situation as they have no therapeutic potential and the barium will obscure future attempts at endoscopic intervention. While high dose continuous infusion intravenous PPI therapy is clearly indicated, in the presence of active bleeding, selective second-look endoscopy is both cost-effective and more likely to control hemorrhage. Routine second-look endoscopy is not a cost-effective strategy in patients who respond to initial dual modality (high dose PPI therapy plus dual modality endoscopic) therapy.

Answer C

Re-bleeding from high-risk peptic ulcers (active bleeders and non-bleeding visible vessels) can be significantly reduced by combination therapy consisting of dual modality endoscopic intervention (epinephrine injection plus cautery) in addition to high dose intravenous PPI therapy (an 80 mg bolus followed by 8 mg/hr for up to 72 hours). High dose intravenous PPI therapy and endoscopic therapy alone are both less effective than combination therapy.

Answer B

The MELD score was developed to predict survival in patients following placement of TIPS. This has recently been adopted by UNOS to identify patients at high risk for mortality while awaiting liver transplantation and to prioritize patients on the active liver transplant waiting list. OF numerous variables assessed to derive this score only the bilirubin, INR and serum creatinine were shown to be significant in multivariate analysis.

Answer C

Cutaneous malignancies, all type of B cell lymphomas and Kaposi sarcoma are more common in organ transplant recipients than the general population. The incidence of colon carcinoma, even in patients with UC, is not increased compared to the general population.

Answer B

Diarrhea is not observed more commonly in transplant recipient than in the general population. However, the development of chronic diarrhea in a liver transplant recipient should be investigated including full colonoscopy with biopsy for viral fungal, mycobacterium and parasite etiologies.

Answer B

Microvesicular steatosis as a cause for fulminant hepatic failure is most commonly attributed to use of valproic acid. However, this histologic picture may also be seen in patients with Reye’s syndrome. A mixture of micro and macro vesicular steatosis can also be seen with tetracycline.

Answer D

Cirrhosis is not a risk factor for the development of toxicity to any given drug. Individuals with cirrhosis actually metabolize drugs at a slower pace and therefore produce active metabolites at a much slower rate than do otherwise healthy individuals. Thus, metabolites that are associated with intrinsic toxicity are produced more slowly and have time to be metabolized. Idiosyncratic reactions have no relationship to rate of metabolite production and therefore the presence has no bearing on whether such agents will develop toxicity or not.

Answer B

PBC and PSC are both immunologic disorders. Approximately 20% of patients are ANA positive. Although PSC involves large bile ducts, they are usually fibrotic and do not dilate to any significant degree. Both disorders are associated with malignancies; PBC with breast carcinoma and PSC with cholangiocarcinoma and colon cancer. URSO has been shown to be beneficial in PBC and typiclly leads to a reduction in AST, ALT and ALP, improves liver histology in patients with stage I and II disease and reduces mortality and the need for liver transplantation in patients with cirrhosis. In contrast, two randomized controlled trials have not demonstrated any benefit in biochemistry, liver histology or mortality in patients with PSC.

Answer C

Option A

Option B

Option A.

NNT = 1/20% = 1/.20 = 5. NNT= the inverse of ARR.

Option B.

Resting anal pressures are largely a result of the myogenic tone of the internal anal sphincter which is not affected in patients with multiple sclerosis. Decreased pressures are seen in many diabetic patients (although not all) with fecal incontinence, presumably due to autonomic dysregulation. In systemic sclerosis, the IAS (internal anal sphincter) is frequently thin and fibrotic whereas lateral sphincterotomy surgically incises the IAS to reduce tone and allow anal fissures to heal.

Option C.

Of the more than 30 peptides and hormones identified, neurotransmitter functions have been defined for only five; these are acetylcholine, substance P, and serotonin (excitatory) and nitric oxide and VIP (inhibitory).

Option C.

5HT4 agonists act to increase gastrointestinal transit and are contraindicated in patients with diarrhea. Tegaserod has been found to be effective only in women with IBS and constipation predominance.

option B.

Melanosis coli is a benign pigmentation of the colonic mucosa which occurs in association with longstanding use of anthraquinone laxatives such as cascara, senna and aloe. It is reversible when exposure to these laxatives is stopped. Magnesium citrate is a saline laxative whereas bisacodyl and phenolphthalein belong to the diphenylmethane family which does not produce melanosis.

Option D.stimulation of alpha adrenergic receptors

Answer is (c), 75% in most recent series.

Answer C.

Alcoholism, cirrhosis, longer duration of infection, genotype 1, and high viral loads are associated with diminished responsiveness. Short duration of infection, genotypes 2 and 3, and low viral levels are linked to a greater likelihood of a therapeutic response.

The answer is d

The most common liver disease in pregnancy is viral hepatitis. It is usually asymptomatic and presents as abnormal liver enzymes. Although gallstones are common, they do not cause problems in the majority. The other disorders are uncommon.

The answer is D.

Patients with small duct pancreatitis in contrast to those with large duct chronic pancreatitis, which is largely related to alcohol, do not progress to steatorrhea, in fact these patients, observed over many years always have chronic abdominal pain as their symptom. Small duct pancreatitis is usually not caused by alcohol. Alcohol abuse leads to large duct chronic pancreatitis. Small duct chronic pancreatitis is often in the category of idiopathic chronic pancreatitis. Calcifications are very uncommon in patients with small duct chronic pancreatitis in marked contrast to those with large duct chronic pancreatitis. Unexplained abdominal pain in a patient in must lead to the high suspicion that this could be CT scan negative and sometimes ERCP negative, chronic pancreatitis of the small duct variety. Such patients are best detected by a hormone stimulation test such as a secretin test. The secretin test is only done in about 10 centers throughout the United States, but by far, is the best test to detect such pancreatitis when radiographic examinations are normal. EUS may have a role in this regard, but at the present time, it appears that EUS cannot be recommended as a consistent diagnostic test in such patients suspected of having small duct chronic pancreatitis. Recent studies have compared the sensitivity and specificity of patients who ultimately are shown to have small chronic pancreatitis with a secretin test and in at least two studies done at two independent university medical centers, the sensitivity was about 55% and the specificity about 60% in comparing EUS to the secretin test.

The answer is C.

Although clinicians are quite adept at lowering cholesterol now that so many excellent medications within the statin family are available, it is not generally appreciated by most practitioners that the statins are not very effective in lowering triglyceride levels once they reach to a level of 500mg percent or higher. Those patients susceptible to getting acute pancreatitis of chronic pancreatitis form high triglyceride levels in the blood must have that triglyceride level lowered below 500mg percent. Most of these patients who have such high triglyceride levels are diabetics I in poor control. Therapeutic efforts must be madeto get as tight control of glucose metabolism as is possible, put such patients on a low fat diet, and most importantly, lower the triglyceride level with gemfibrozil in doses of 600mg three times a day. Niacin preparations whether they be short-acting or long-acting are not to be utilized in lieu of gemfibrozil. Such preparations have side effects, sometimes serious, and have not been very effective in the average patient.

Option B

Sympathetic nerves are important for pain and for inhibition of pancreatic stimulation. Parasympathetic nerves include the vagus and postganglionic nerves. Both sympathetic and parasympathetic pass through the celiac plexus.

The correct answer is A. Macrovesicular steatosis

The Correct Answer is C. Gastroparesis

• Chronic progressive liver disease; > 90% women; 30-65 years
• Characterised by destruction of intrahepatic bile ducts, portal inflammation and scarring, leading relentlessly to cirrhosis and liver failure
• Presence of granulomata in portal tracts.
• Both B and T cells found; both CD4+ and CD8+
• Failure of biliary secretion leads to retention of toxic substances and hence secondary chemical damage to hepatocytes.
• Induction of class II expression on both biliary epithelium and hepatocytes: exacerbated immune mediated damage.
  
• May be asympomatic for some time

1. Signs of portal hypertension: hepatomegaly, splenomegaly, variceal bleeds, ascites
2. Signs of cholestasis: pigmentation, gallstones, steatorrhoea, pruritis, jaundice
3. Abdominal pain
4. Osteoporosis (important co-existing problem; steroids contra-indicated as can exacerbate this)
5. Associated with other auto-immune diseases: e.g. Sjogren's syndrome; thyroid auto-immunity; SLE; scleroderma; rheumatoid arthritis; CREST; dermatomyositis; renal tubular acidosis

• Increased prevalence of hepatocellular cancer and breast cancer
  
• Less rapid disease progression: asymptomatic patients and those with hepatic granulomas
  
• More rapid disease progression: symptomatic, older, hepatomegaly, high bilirubin, low albumin, cirrhosis
  
• Some chronic hepatitis patients are anti-mitochondrial antibody positive, and have a mixed clinical pattern.
  
• Some primary biliary cirrhosis may present at the cirrhotic stage, with raised anti-mitochondrial antibody levels
  
• Almost all patients who have anti-mitochondrial antibodies will go on to develop primary biliary cirrhosis
  

• Auto-antibodies
• Raised serum immunoglobulin: IgM
• Complement activation
• T cells: decrease in number as disease progresses
• Possible association with HLA-DR8
• (Raised bilirubin, alkaline phosphatase and lipids)
  

• Granulomas
• Increased expression of class I MHC on bile duct epithelial cells
• Aberrant expression of class II MHC on bile duct epithelial cells
• T cell infiltrate around the bile ducts – CTL may be early event, but more usual to see CD4+ T cells seen around the bile ducts.
• Excess IgM producing B cells around the bile ducts.
• Features have been said to resemble either (i) graft - versus - host disease; or (ii) transplant rejection.
• (Accumulation of excess copper)
  

1. symptomatic relief [including anti-cholestatic (urosodexycholic acid, which may provide symptomatic relief but does not affect prognosis) and anti-pruritic agents]
2. immunomodulatory and immunosuppressive agents [steroids, azathioprine, cyclosporin, FK506, penicillamine; colchicine, methotrexate] have all been attempted but have not been shown to be effective
3. transplantation for end-stage disease