Exam II

Question 1

Nutrition: Energy comes from carbs, fats, and proteins for daily metabolic needs, while vitamins and minerals function as coenzymes or hormones in vital metabolic pathways.

Malnutrition occurs when there is an insufficiency in the diet. Differentiate between primary and secondary malnutrition

Answer 1

1. Primary
   - -one or all components missing from diet
2. Secondary
   - -malabsorption
   - -impaired use or storage
   - -excess loss
   - -inc. need for nutrients

Question 2

Nutrition: Several conditions may contribute to malnutrition including:

1. poverty/homelessness
2. older patients
3. children
4. trace nutrient deficiencies
5. self-imposed dietary restrictions (anorexia)
6. failure of supplementation (infants, pregnancy)

Infection and illness can also play a role in malnutrition. Explain their roles

Answer 2

1. Infection
   - -contribute to or casues
2. Acute/Chronic illness
   –accelerates basal metabolic rate
   –increases daily requirements
   “sick” people less likely to eat (effect of acute phase release)

Question 3

Nutrition: Chronic alcoholism is a major contributor to malnutrition as it results in:

a. vit. deficiencies (thiamine, pyridoxine, folate, Vit. A)
b. defective GI absorption
c. abnormal nutrient utilization and storage
d. increased metabolic needs

Answer 3

All of the above

AND:

• increased rate of loss
• -irreversible brain damage (Wernicke encephalopathy; Korsakoff psychosis)

Question 4

Nutrition: Protein energy malnutrition (PEM) is a lethal disease that MC affects children. It may either result from inadequate intake of proteins/calories OR from deficiencies in the digestion or absorption of proteins.

What can PEM lead to?

a. loss of fat and muscle
b. weight loss
c. lethargy
d. generalized weakness

Answer 4

all of the above

• reduced heart and lung capacity
• dec. metabolic rate
• edema, immunodeficiency, etc.

Question 5

Nutrition: True/False - PEM is common in low resource countries. It is the major factor for high death rates among children younger than 5 y/o in these countries. However, in developed countries, it often occurs in older, debilitated patients or children who live in poverty.

Answer 5

True

Question 6

Nutrition: Malnutrition is determined based on BMI (weight in kg/height m2).

What indicates malnutrition?

Answer 6

1. BMI < 16kg/m2 (normal 18.5-25)
2. weight , 80% of normal
   * weight loss may be masked by edema (e.g. Kwashiorkor)
3. evaluation of fat stores (thickness of skin folds)
4. muscle mass (reduced circumference of mid arm)

Question 7

Nutrition: Plasma proteins may be another key in identifying malnutrition. Albumin and transferrin levels provide a measure of the adequacy of the visceral protein compartment.

What other proteins might be useful in determining malnutrition?

Answer 7

pre-albumin (tranthyyrein); C-reactive protein

Question 8

Nutrition: Marasmus and Kwashiorkor affect malnourished children. They can present as a range of clinical syndromes, but are characterized by a dietary intake of protein and calories that inadequately meet the body’s needs.

These disorders indicate depletion of different protein compartments in the body. Distinguish b/t the two

Answer 8

1. Marasmus
   –protein in SK muscles
   (somatic compartment)
2. Kwashiorkor
   –protein in viscera (liver)
   (visceral compartment)

Question 9

Nutrition: ______ is suspected when:

1. weight < 60% of normal (sex, age, height)
2. restricted growth
3. loss of muscle (catabolism of somatic compartment)
4. mobilization of subcutaneous fat (used as fuel)

Answer 9

Marasmus

• aa’s = source of energy
• visceral compartment = precious, marginally depleted
• plasma albumin = normal or slightly reduced

Question 10

Nutrition: In children with marasmus, production of leptin is low. This may stimulate the HPA axis to produce high levels of ______ contributing to lipolysis

Answer 10

cortisol

**Buzzword for marasmus: Muscle wasting

Question 11

Nutrition: Children with marasmus appear emaciated due to significant loss of muscle and subcutaneous fat.

Other common signs/symptoms include which of the following?

a. enlarged head
b. anemia
c. immune deficiencies

Answer 11

all of the above

• large head
• anemia
• Vit. deficiencies
• immune deficiencies (T-cell) = inc. infection, inc. nutritional demands

Question 12

Nutrition: Kwashiorkor is characterized by protein deprivation (more severe than caloric deficits). It is most commonly seen in African children who have been weaned too early and subsequently fed a carbohydrate diet.

Less severe forms may occur worldwide. What are examples of this (clinical manifestations)?

Answer 12

1. chronic diarrhea (malabsorption of protein)

2. chronic protein loss (nephrotic syndrome; extensive burns)

Question 13

Nutrition: Kwashiorkor is characterized by marked protein deprivation (notably visceral protein). It results in

1. hypo-albuminemia (dependent anemia)
2. inc. fluid retention (masks weight loss)
3. sparing of subcutaneous fat and muscle mass

Children may also have disorders of the hair and skin. What are examples?

Answer 13

1. Hair
   - -sparse
   - -loss of color
   - -alternating bands - pale and dark
2. Skin
   - -characteristic scaly lesion “flaky paint”
   - -alternating zones of hyperpigmentation and hypopigmentation w/ desquamation

NUTSHELL: edema (swelling of the belly), anemia, hepatosteatorrhea, skin lesions

Question 14

Nutrition: A 3 year old Nigerian girl is brought to the clinic with complaints of loss of appetite, apathy and listlessness.

On PE you note edema of the abdomen, enlarged, palpable (fatty) liver and alternating bands of pale and dark hair with “flaky paint” skin.

Labs reveal
1. Dec. albumin

You suspect

Answer 14

Kwashiorkor

• defects in immunity = inc. 2ndary infections
• spares subcutaneous fat and muscle

NOTE: Kwashiorkor (loss of protein) vs. Marasmus (loss of all nutrients)

Question 15

Nutrition: Unlike marasmus, Kwashiorkor presents with an enlarged fatty liver (hepatic steatosis; but cirrhosis is rare). In addition, the small bowel undergoes changes such as:

a. dec. mitotic index of crypts of the glands
b. mucosal atrophy
c. villous atrophy
d. ulceration

Answer 15

A-C

• dec. mitotic index
• mucosal atrophy
• loss of villi and microvilli

*Tx can reverse changes

Question 16

Nutrition: Bone marrow in both kwashiorkor and marasmus may be hypoplastic. This is mainly due to decreased numbers of red cell precursors.

Mild-moderate anemia may also be detected in peripheral blood. This is due to what?

Answer 16

Multi-factorial

1. nutritional deficiencies = Fe2+, folate, protein
2. suppressive Effects of infection (anemia of chronic disease)

Question 17

Nutrition: True/False - Children with kwashiorkor and marasmus may show cerebral atrophy with reduced number of neurons and impaired myelinization of white matter.

Answer 17

True

Question 18

Nutrition: Both anorexia nervosa and bulemia tend to occur in previously healthy patients.

1. ______ is self induced starvation. It has the highest death rate of psychiatric disorders.
2. ______ binging on food and inducing vomiting

Answer 18

1. Anorexia nervosa
   - -similar to PEM
   - -amenorrhea is Dx feature (dec. GnRH, dec. LH and FSH)
2. Bulemia

Question 19

Nutrition: Individuals with anorexia or bulemia tend to have decreased thyroid hormone release. What are features of this?

Answer 19

• cold intolerance
• bradycardia
• constipation
• skin and hair changes

Question 20

Nutrition: Individuals with anorexia or bulemia tend to have decreased thyroid hormone release.

What are other common findings?

Answer 20

• dehydration/electrolyte issues
• dry/scaly skin
• dec. bone density (low E2; mimick post-menopausal osteoporosis)
• anemia, hypoalbuminemia

Question 21

Nutrition: What is a MAJOR complication of anorexia nervosa (also bulemia)?

a. increased susceptibility to cardiac dysrhythmia and sudden death
b. nephrotic syndrome
c. enlarged veins due to stasis
d. none of the above

Answer 21

Increased cardiac dysrhythmia

*hypokalemia

Question 22

Nutrition: 13 vitamins are necessary for health.

1. The fat soluble vitamins are _____ and are readily stored in the body. They are poorly absorbed in malabsorption disorders.
2. ____ can be synthesized endogenously.

Vitamin deficiency may be primary (dietary) or secondary (to disturbances in intestinal absorption, transport in blood, tissue storage, or metabolic conversion).

Answer 22

1. ADEK
2. • -Vit. D - sun exposure (steroids)
   • Vit. K - biotin (intestinal microflora)
   • Niacin (tryptophan)

Question 23

Nutrition: The major function of this vitamin is to:

1. maintain normal vision
2. regulate (epithelial) cell growth and differentiation
3. regulate lipid metabolism
4. inc. host resistance to infections

Answer 23

Vit. A

*maintain integrity of epithelium and stimulate immune system

NOTE: infection may reduce bioavailability (inhibit retinol/acute phase response)

Question 24

Nutrition: Vitamin A (retinoids) is a group of related compounds that may/may not have same biologic activity.

It comes from the diet (animal-derived foods) such as liver, fish, eggs, milk and butter. It can also come from carotenoids (B-carotene) that gets converted to Vit. A in the body. What are sources of carotenoids?

Answer 24

carrots, squash, spinach

Question 25

Nutrition: Because Vitamin A is a fat-soluble vitamin, it requires bile and pancreatic enzymes for absorption. It is absorbed in the intestine (site of conversion of B-carotene to retinol) and then transferred to the liver via chylomicrons. In the liver, it is esterified and stored.

How does uptake occur in the liver? Where in the liver is Vit. A stored?

Answer 25

Uptake: apolipoprotein E

Storage: perisinusoidal stellate (Ito) cells
*6 mos storage

Question 26

Nutrition: True/False - In children, stores of vitamin A can be depleted in the presence of infections. Furthermore, vitamin A absorption is poor in infants.

In adults, malabsorption syndromes, bariatric surgery, and chronic use of mineral oil as a laxative are causes for malabsorption.

Answer 26

True

Question 27

Nutrition: Which of the following is affected by a deficiency in Vitamin A?

a. ocular epithelium
b. lining of upper respiratory tract
c. urinary tract
d. epidermis

Answer 27

all of the above

1. ocular
   - -night blindness
2. upper resp. lining
   - -loss of mucociliary (inc. 2ndary pulm. infections)
3. Urinary tract
   - -renal/urniary stones from desquamated keratin debris
   - -squamous metaplasia
4. Epidermis
   - -hyperplasia and hyperkeratinization
   - -plug ducts of adrenal glands – dermatosis
5. immune deficiency

Question 28

Nutrition: A patient presents with headache, dizziness, vomiting and blurred vision. Her fiance states that she was complaining of bone and joint pain, was refusing to eat, and that she has been in a stupor for the past couple of hours. He suspects a brain tumor (pseudomotor cerebri; intracranial HTN w/ papilledema).

On PE you note dry skin and cracked lips. Liver is palpable.

He states she eats lots of carrots, spinach and squash, and takes supplements for fat soluble vitamins. What do you suspect?

Answer 28

Vitamin A toxicity

• -HA, dizziness, vomiting, stupor, blurred vision
• -confusion
• -weight loss, anorexia, bone/joint pain (chronic loss increases osteoclasts; inc. risk fractures)

Question 29

Nutrition: Vitamin A is contraindicated in pregnancy. Why?

Answer 29

Retinoic acid is a teratogen

Question 30

Nutrition: What are clinical uses for Vitamin A?

a. severe acne
b. forms of psoriasis
c. treatment of acute promyelocytic leukemia
d. colon cancer

Answer 30

A-C

Question 31

Nutrition: Vitamin C (Ascorbic acid) functions in many biosynthetic pathways by accelerating hydroxylation and amidation reactions.

It is best known for its role in activating prolyl and lysyl hydroxylases of pro-collagen. What would you expect of inadequately hydroxylated procollage?

Answer 31

*cannot acquire stable helical confirmation

• poorly secreted from fibroblast
• inadequate cross-linking
• lack of tensile strength
• more soluble/vulnerable to degradation

Question 32

Nutrition: True/False - Vitamin C can act indirectly by regenerating the antioxidant form of Vitamin E

Answer 32

True

Question 33

Nutrition: Vitamin C is NOT synthesized endogenously and must be obtained by the diet. Thus, deficiency leads to scurvy (uncommon because most diets supply enough). Scurvy is characterized as:

1. bone disease in growing children
2. hemorrhages and healing defects in both children and adults

What are common symptoms associated with scurvy?

Answer 33

1. Inc. bleeding
   - -skin, gums, periosteum and joints
   - -poor vessel support (lack collagen)
2. inadequate synthesis of osteoid
3. impaired wound healing

Question 34

Nutrition: What are the sources of vitamin C?

Answer 34

milk, liver, fish, fruits (limes), vegetables

Question 35

Nutrition: True/False - The contention that Vitamin C protects against the common cold or helps mitigate symptoms has NOT been supported by clinical studies. However, mild symptom relief may occur from histamine within ascorbic acid.

There is also NO evidence that Vitamin C protects against cancer development

Answer 35

True

Question 36

Nutrition: True/False: Toxicities related to high doses of Vitamin C are rare but can occur (MC calcium oxalate kidney stones). This is due to limited physiologic availablility of Vitamin C. It is inherently unstable, is poorly absorbed and is rapidly excreted

Answer 36

True

Question 37

Nutrition: Deficiency of this vitamin is seen most often in alcoholic patients. Classic findings include oral-ocular-genital.

1. Lips with angular cheilitis (petechiae) and cheliosis
2. Atrophic and magenta tongue
3. Seborrheic-like dermatitis (w/ follicular keratosis around nares and face)
4. Genital dermatitis in men
5. Confluent dermatitis of the scrotum (spares midline; extends to thighs)

Answer 37

Vitamin B2 (riboflavin)

Ceilitis: chapped lips

NOTE: dramatic response to repletion

Question 38

Nutrition: Niacin is obtained by dietary sources (animal, proteins, eggs, milk and vegetables).

True/False - Niacin deficiency most often results from a deficiency of nicotinic acid (niacin, B3) or its precursor aa tryptophan.

Answer 38

True

Question 39

Nutrition: True/False - Niacin deficiency may coexist with other vitamin deficiencies, especially those that interfere with the conversion of tryptophan to niacin (pyridoxine)

Answer 39

True

Question 40

Nutrition: Niacin deficiency (Pellagra) is most often associated with a diet composed of corn, millet or sorghum. It can occur within 60 days of dietary niacin deficiency. Medications may also cause Pellagra. List examples

Answer 40

Medications:

1. Isoniazid, Azathioprine (6-mercaptopurine metabolits), 5-fluorouracil, ethionamide, pyrazinamide
2. Anti-convulsants
3. Alcoholism (MC developed countries)

Question 41

Nutrition: Other possible causes of pellagra include:

a. carcinoid tumors
b. Hartnup disease
c. gastrointestinal disorders
d. hyperkalemia

Answer 41

A-C

• carcinoid tumors (divert tryptophan to 5HT)
• Hartnup disease (impaired trp aborption)
• GI disorders (Crohn, GI surgery)
• Prolonged IV supplementation
• Psychiatric; anorexia nervosa
• Restrictive diets in “food allergy” patients (atopic derm.)

Question 42

Nutrition: A patient presents with:

1. Diarrhea
2. Dementia
3. Dermatitis (“casal necklace”)

others: loss of appetite, weakness, mental depression, photosensitivity, neurologic (can be w/out skin changes), depression, hallucinations, coma, etc.

Answer 42

Niacin deficiency (B3)

*“Casal necklace” = photosensitive eruption
(symmetrical pellagrous skin on face, neck, upper chest, extensor arms, backs of hands)

NOTE: pellagrous skin takes 4x longer to recover from acute phototoxic injury

Question 43

Histo: The liver is located in the RUQ deep to ribs 7-11. It crosses the midline.

The _______ surface of the liver is dome shaped, separated into R. and L. lobes and moves with the regular movements of the diaphragm.

Answer 43

Diaphragmatic surface

• falciform and coronary ligaments
• smooth surface (visceral peritoneum except site in direct contact with diaphragm)

Question 44

Histo: The ______ surface of the liver has impressions from contact with other organs.

It is covered by serosa (visceral peritoneum) except at the hilum (entry/exit of vessels and nerves) and the contact site with the gallbladder.

Answer 44

Visceral surface

Question 45

Histo: Describe the innervation of the liver

Answer 45

1. Sympathetic
   - -blood vessels
   - -inc. symp – inc. vascular resistance – dec. liver blood volume
2. Parasympathetic
   - -large ducts/blood vessels
   - -stimulation – glucose uptake

Question 46

Histo: The hepatic portal vein supplies 75-80% of blood to the liver. It collects blood from the stomach, spleen, pancreas and intestines.

True/False - It is oxygen rich and nutrient poor.

Answer 46

False

• nutrient rich, toxin rich, hormone rich (enteroendocrine and pancreas)
• O2 poor
• RBC’s and break-down products (spleen)

Question 47

Histo: The hepatic artery is a branch of the celiac artery that supplies 20-25% of blood to the liver.

True/False - It is oxygen-rich and nutrient and toxin-poor.

Answer 47

True

*hepatic artery carries arterial blood

Question 48

Histo: Branches of the portal venule and hepatic arteriole run together as 2 of 4 components of the portal triad.

List the components

Answer 48

1. Portal vein
2. Hepatic artery
3. Bile duct
4. Lymphatic vessel

Question 49

Histo: Describe blood flow through the liver

Answer 49

1. Portal vein/Artery mix in the sinusoids
2. Enter Central vein
3. Sublobular veins
4. L and R. hepatic veins
5. Empties into Inferior vena cava

Question 50

Histo: True/False - The portal vein and hepatic artery branch and send these branches into various regions/lobes. The branching pattern of these vessels allows each lobe (8 in total) to be independent, surgically resectable segments.

Answer 50

True

Question 51

Histo: There are 3 models that describe the liver lobule:

1. Classical
2. Portal
3. Liver Acinus

The _______ describes the anatomical distribution of vessels and path of blood flow through the lobule. The central vein is at the center. The portal triad is at hexagon angles.

Answer 51

Classical

Question 52

Histo: There are 3 models that describe the liver lobule:

1. Classical
2. Portal
3. Liver Acinus

The _____ describes bile flow in the liver (central vein – bile duct). The bile duct is at the center of the portal lobule. The boundaries are imaginary lines from 3 central veins closest to the bile duct.

Answer 52

Portal lobule

Question 53

Histo: There are 3 models that describe the liver lobule:

1. Classical
2. Portal
3. Liver Acinus

The functional unit of this model is the liver lobule (diamond shaped.) It describes exocrine secretory functions (bile) and shows hepatocytes in 3 zones (concentric circles).

Answer 53

Liver acinus

Boundaries:

1. Central vein to Portal triad
2. Central vein to portal triad
3. back to central vein

Question 54

Histo: This zone of the liver acinus is closes to the short axis. It is closest to nutrients and toxins (via portal) as well as oxygenated blood (arterial).

It is the first zone to show morphological change from the blockage of bile ducts

Answer 54

Zone 1

• last to die w/ circulatory defects; 1st to regenerate
• found on periphery of classic lobule

Question 55

Histo: This zone of the liver acinus is the farthest from the short axis. It is closest to the central vein. It has less access to oxygenated blood, nutrients and toxins.

Answer 55

Zone 3

• first to show ischemic necrosis w/ circulatory issues
• slowest to regenerate

Question 56

Histo: Hepatic sinusoids are composed of discontinuous endothelium (fenestrated) within which are Kupffer cells (macrophages that ingest RBC debris).

In between the sinusoids and the hepatocytes is the perisinusoidal space (space of Disse). What is the function of this space?

Answer 56

site of exchange between blood and hepatocytes

Question 57

Histo: These are the major cells of the liver. They are polygonal (6-sides) in shape and contain a lot of mitochondria (stain eosinophilic).

They also contain important organelles necessary for proper liver function including: peroxisomes, rER, sER, glycogen, lipid droplets and lysosomes.

Answer 57

Hepatocytes

• 2 sides (basal surface) face perisinusoidal space
• 4 sides (lateral surface) face neighboring hepatocytes and bile canaliculus (apical surface)

Question 58

Histo: Bile travels from hepatocytes to the gallbladder and finally to the duodenum. It flows through the bile canaliculi (grooves in the hepatocyte surface) into the bile duct which is lined by ____________. These cells are responsible for contraction and unidirectional bile flow.

Answer 58

Cholangiocytes

Question 59

Histo: Explain the direction of bile flow from the liver to the gallbladder

Answer 59

1. Bile canaliculus
2. Bile duct
3. R and L. hepatic ducts
4. Common hepatic duct
5. Cystic duct
6. gallbladder

Question 60

Histo: Explain the direction of bile flow from the gallbladder to the duodenum

Answer 60

1. Extrahepatic duct
   - -carries bile out of the gallbladder
2. Cystic duct
3. Common bile duct
4. Duodenum

Question 61

Histo: Red blood cells are converted to unconjugated bilirubin by first being converted to heme. Once the unconjugated bilirubin is formed, it enters plasma, binds albumin and forms an unconjugated bilirubin-albumin complex (indirect bilirubin). This complex enters the liver where it is conjugated to bilirubin by ________.

Answer 61

Conjugated by glucuronic acid

• enters gut – bacteria break it down to free bilirubin
• turned to urobilinogen – excreted in feces

Question 62

Histo: Which of the following are functions of the liver?

a. bile production
b. bilirubin conjugation
c. glucose metabolism
d. hemopoiesis in fetus/newborns
e. ethanol metabolism

Answer 62

all of the above

• iron metabolism, storage
• cholesterol synthesis
• gluconeogenesis
• cholesterol synthesis
• plasma protein syntehsis
• IgA synthesis
• storage/modification of ADEK

Question 63

Histo: Bile plays a role in which of the following?

a. absorption of fat
b. excretion of cholesterol
c. excretion of bilirubin, iron and copper

Answer 63

all of the above

Question 64

Histo: True/False - 90% of bile salts are reabsorbed by the gut and returned to the liver (portal blood) where they are reabsorbed and secreted by hepatocytes

Answer 64

True

Question 65

Histo: Bile flow is regulated hormonally and neurally. It is controlled by:

1. CCK, gastrin, motilin
2. estrogen (pregnancy)
3. parasympathetic stimulation

Explain how these hormones/neural stimulation affect bile flow

Answer 65

1. CCK, gastrin, motilin – increase bile flow
2. estrogen – decrease bile secretion
3. parasympathetic – contraction of gallbladder; relaxation of sphincter of Oddi

Question 66

Histo: The gallbladder is located in the depression on the liver’s visceral surface.

There are 3 anatomical regions:

1. Fundus
2. Body
3. Neck

The ____ is the wide blunt end located at the tip of the R. 9th costal cartilage.

Answer 66

Fundus

• body = main region
• neck = narrow end joins cystic duct

Arterial supply: cystic artery
Venous drainage: cystic veins

Question 67

Histo: True/False - The function of the gallbladder is to store and concentrate bile. Dilute bile from the cystic duct is removed of water leading to a 10-fold increase in concentration of bile salts, cholesterol and bilirubin.

Answer 67

True

Question 68

Histo: ________ describes the formation of diverticula in the mucosa. This is due to hyperplasia and herniation of epithelial cells through the muscularis. It results in chronic inflammation from bacteria, and increased risk of gallstone formation.

Answer 68

Rokitanski-Aschoff sinuses

Question 69

Histo: Concentration of bile depends on the presence of lateral plications between epithelial cells (cholangiocytes) that form an intercellular space.

Laterally localized Na/K+ pump moves Na into these lateral intercellular spaces, and water follows. This enables the formation of concentrated bile _____ channels at the apical and basolateral membranes.

Answer 69

aquaporin channels

AQP1 and AQP8

*hydrostatic pressure in lateral intercellular space – isotonic fluid moves into laminal propria – fenestrated capillaries

Question 70

Histo: The muscularis of the gallbladder is composed of SM and elastic fibers. Contraction of the SM ______ the volume of the gallbladder, forcing bile to exit via the cystic duct.

Answer 70

decreases

Question 71

Histo: The gallbladder and pancreas secrete products into the duodenum. What are these products?

Answer 71

1. gallbladder
   - -bile (from liver)
2. pancreas
   - -inactive digestive enzymes (zymogens)
   - -HCO3-

Question 72

Histo: The pancreas is a retroperitoneal structure that overlies and crosses L1 and L2.

It is composed of 4 parts:

1. Head
2. Neck
3. Body
4. Tail

The main pancreatic duct starts in the _____ and ends at the _____ of the pancreas. This duct unites with the bile duct at the hepatopancreatic ampulla (Vater).

Answer 72

starts in the tail and ends at the head

Question 73

Histo: Within the pancreas are scattered endocrine cells (islets) and pancreatic acinar cells.

______ cells are two-toned. They have basophilic nuclei (basal region; rER) but have eosinophilic granules apically.

Answer 73

Pancreatic acinar cells

Question 74

Histo: Intercalated ducts begin within the acinus (secretory unit). They are lined with ________ cells. These cells are poorly stained with eosin. They secrete lots of fluid (1L/day), Na and HCO3-.

Answer 74

centroacinar cells

*drain into intralobular — interlobular – main pancreatic duct

Question 75

Histo: Pancreatic exocrine secretion is regulated by Secretin, CCK, the SNS and PNS.

Describe effects of each

Answer 75

1. Secretin
   - -inc. HCO3 and H2O from centroacinar cells
2. CCK
   - -inc. pancreatic digestive enzymes from acinar cells
3. SNS
   - -blood flow
4. PNS
   - -inc. both acinar and centroacinar

Question 76

Physio:

1. The hepatic artery acquires ______ blood from general circulation.
2. The portal vein obtains _____, nutrient-rich blood from the GI tract
3. The hepatic vein carries blood from the liver to the _____

Answer 76

1. oxygenated
2. deoxygenated
3. IVC

Question 77

Physio: List the cells of the liver

Answer 77

1. Biliary (cholangiocytes) - line bile ducts
2. Sinusoidal (endothelial) cells
3. Kupffer (macrophages)
4. Lymphocytes – immune cells
5. Stellate (Ito) cells

Question 78

Physio: The portal acinus is coordinated into 3 different lobules (models):

1. Classic hepatic lobule
2. Portal lobule
3. Portal acinus

_____ drains blood from the portal vein and the hepatic artery to the hepatic vein or central vein.

Answer 78

Classic hepatic lobule

Question 79

Physio: The portal acinus is coordinated into 3 different lobules (models):

1. Classic hepatic lobule
2. Portal lobule
3. Portal acinus

______ supplies oxygenated blood to hepatocytes

Answer 79

portal acinus

Question 80

Physio: The portal acinus is coordinated into 3 different lobules (models):

1. Classic hepatic lobule
2. Portal lobule
3. Portal acinus

___ drains bile from hepatocytes to the bile duct

Answer 80

portal lobule

Question 81

Physio: These cells are closest to the portal triad. They are the first to receive O2, nutrients and toxins. They are most resistant to circulatory compromise.

They undergo oxidative metabolism and possess more mitochondria.

Answer 81

Periportal (zone 1) cells

• Krebs, B-ox, gluconeogenesis, glycogen breakdown
• proteosynthesis

Question 82

Physio: These cells are located around the central vein. They are the farthest from the portal triad and receive less O2, nutrients and toxins. They have higher reductive metabolism (e.g. ketogenesis).

They are typically the first cells to die in hepatic ischemia and the first cells to show fatty accumulation.

Answer 82

Perivenous/Centrilobular (zone 3) cells

• glycolysis, glyogen synthesis
• lipid synthesis, biotransformation processes

Question 83

Physio: Hepatic processing occurs in 4 steps:

1. Uptake from blood (sinusoid)
2. Cellular transport (basolat. membrane) into the hepatocyte
3. Processing (ER or Golgi modification; conjugation)
4. Export from the cell (secreted apically to bile.

List the transporters involved in housekeeping/maintaining these processes

Answer 83

1. Na/K+ pump (basolat. membrane)
2. Ca2+ pump (basolat.)
3. Na/H+ antiport (NHE)
4. Na/HCO3- cotransport

RMP = -30 to -40 mV
K and Cl- channels

Question 84

Physio: List the transporters involved in:

1. uptake of bile acids
2. secretion of bile acids

Answer 84

1. Uptake
   - -NTCP (conjugated bile acids)
   - -diffusion
   - -OATPs (bile acids into hepatocytes)
2. Secretion
   - -MRP2
   - -BSEP
   * *transport into bile canaliculus

NOTE: unconjugated = lipophilic

Question 85

Physio: Transport of other organic anions involves the _______. It involves anion exchange via Cl-, glutathione and others.

It has a broad specificity for various substances.

Answer 85

organic anion transport polypeptide (OATPs)

Question 86

Physio: Organic cations are transported by what means?

Answer 86

1. OCT1 and OCT2
2. OATP-A

*drugs, toxins, anesthetics

Question 87

Physio: List the functions of the following basolateral transporters

1. NTCB
2. OATP
3. OCT/OATP-A

Answer 87

1. NTCB (basolateral membrane)
   - -uptake bile acids from blood
2. OATP (basolateral membrane)
   - -uptake bile acids and xenobiotics from blood
3. OCT/OATP-A (basolateral membrane)
   - -uptake of organic cations from blood

Question 88

Physio: List the functions of the following apical transporters

1. BSEP
2. MDR3
3. MDR1
4. ABC5/ABC8
5. CMOAT

Answer 88

1. BSEP
   - -secrete bile acids into bile
2. MDR3
   - —flippase
   - -adds PL choline into bile
3. MDR1
   - -secretes cationic drugs into bile
4. ABC5/8
   - -secretes cholesterol into bile
5. cMOAT
   - -secrete lithocholic acid and bilirubin

Question 89

Physio: Bilirubin handling by the liver starts with metabolization of aged RBC’s by RES forming bilirubin. Hepatocytes take up the bilirubin and conjugate it with ______. It becomes urobilinogen in the GI tract, and is then oxidized to stercobilin.

Answer 89

*glucuronide

NOTE: urobilinogen becomes urobilin in urine

Question 90

Physio: Biotransformation and detoxification of polar molecules occurs in multiple phases.

In the first phase, a reactive group is added to the compound via oxidation, reduction or hydrolysis. What enzymes mediate this process?

Answer 90

CYP 450

• one O2 atom inserted into substrate
• makes compounds polar = ready for phase 2
• can form free radicals or make toxins more reactive

Question 91

Physio: Physio: Biotransformation and detoxification of polar molecules occurs in multiple phases.

In the first phase, the toxin is made water soluble by adding groups via CYP 450 enzymes. The second phase involves conjugation of the substance to make it excretable by the kidneys or intestine. List the enzymes involved in this phase.

Answer 91

Reactions:

• sulfation, glutathione conjugation
• glucuronidation, acetylation, methylation, aa conjugation

Enzymes:
-transferases and methylases

Question 92

Physio: The liver is metabolically active and highly aerobic. It receives 25-30% of the total blood flow and extracts ~20% of oxygen used by the body. This is due to its many roles, including synthesis and degradation of carbs, lipids and proteins.

The liver is a source (or sink) for glucose. What are its actions in the presence of glucagon? Insulin?

Answer 92

1. glucagon (dec. blood glucose)
   - -gluconeogenesis
   - -glycogenolysis
   - -dec. glycogen storage
2. Insulin (inc. blood glucose)
   - -glycogen synthesis
   - -glycolysis
   - -inc. glycogen storage

Question 93

Physio: The liver plays a major role in synthesis and degradation of carbs, lipids and proteins.

True/False - The liver synthesizes proteins including albumin, blood clotting factors, carriage proteins and angiotensinogen. It is also responsible for metabolism of aa’s and tight regulation of plasma aa levels.

Answer 93

True

Question 94

Physio: the liver plays a major role in the synthesis and degradation of carbs, lipids and proteins.

List the non-essentail amino acids produced by the liver

Answer 94

-Ala, Asn, Asp, Glu, Gln, Gly, Pro, Ser, Cys, Tyr

Question 95

Physio: NH4+ is used to make glutamine. It gets detoxified by ureagenesis.

What are the mechanisms for removal of ammonia by the liver?

Answer 95

1. conversion to urea in periportal hepatocytes

2. conversion to Glu in perivenous hepatocytes

Question 96

Physio: The liver metabolizes lipids via

1. B-oxidation
2. Ketogenesis
3. Lipid synthesis and breakdown
4. Cholesterol metabolism
5. LDL, VLDL, HDL

True/False - The liver is the hub (main site) of cholesterol metabolism

Answer 96

True

*chylomicrons converted to remnants by lipoprotein lipase and sent back to the liver

Question 97

Physio: The liver synthesizes and stores fat soluble vitamins A, D, E, and K.

Where are these vitamins synthesized/stored?

Answer 97

1. Vitamin A
   (retinol and derivatives)
   –Stellate cells
2. Vitamin D
   - -25 hydroxylation in hepatocytes
3. Vitamin E
   - -a-tocopherol and g-tocopherol
4. Vitamin K
   - -important in coagulation

Question 98

Physio: Iron is absorbed in the duodenum, where it binds to transferrin and enters the liver via transferrin receptors.

The majority of Iron is stored in hepatocytes bound to ferritin, though there are small pools of free iron. What happens in the case of hemochromatosis?

Answer 98

Storage capacity for iron is overwhelmed

*liver synthesizes hepcidin to lower plasma Fe levels (reducing absorption)

Question 99

Physio: Copper is absorbed in the jejunum, binds to albumin, and enters hepatocytes via copper transport proteins.

It involves a complex chaperone-transport mechanism in hepatocytes. This mechanisms requires _______.

Answer 99

Requires ceruloplasmin

• Wilson disease - mutation in ATP7B
• most ingested Cu is excreted in bile

Question 100

Large Bowel: _______ occurs from absence of neural crest (ganglion) cells within the colon.

The aganglionic segment fails to relax, causing functional obstruction. Symptoms include: bilious emesis, abdominal distension and failure to pass meconium (within first 48 hours)

Answer 100

Congenital aganglionic megacolon

• always starts at rectum – extends proximally
• loss of coordinated peristaltic contractions

Question 101

Large Bowel: Congenital aganglionic megacolon is beleived to be due to the LOF mutation in the RET proto-oncogene. What is the function of the RET gene? What are risk factors for this mutation?

Answer 101

Fxn:
–growth and differentiation signalling

RF’s:
–Down syndrome

Question 102

Large bowel: What would be seen on a Digital rectal exam (DRE) of a child with congenital aganglionic megacolon?

Answer 102

–lack of stool in rectum OR explosive expulsion of gas and stool

Question 103

Large bowel: True/False - In congenital aganglionic megacolon, the colon proximal to the aganglionic segment becomes dilated. As it becomes dilated there is increased risk of perforation.

Answer 103

True

• dilated segment - ganglion cells present
• narrowed segment - ganglion cells absent

Question 104

Large bowel: Congential aganglionic megacolon can be diagnosed using barium enema and rectal suction biopsy. What do these tests detect? How is this treated?

Answer 104

Dx:

1. Barium enema – localises transition zone
2. Rectal suction biopsy - absence of ganglion cells

Tx: Surgical excision of aganglionic segment

Question 105

Large bowel: Chronic T. cruzi infection (transmitted by Reduviid “kissing bug”) can destroy the neurons of the ENS.

Denervation causes uncoordinated motor activity resulting in abnormal basal colonic motility and impaired relaxation of the anal sphincter. What is the net result?

Answer 105

Constipation

*most cases associated with dilated esophagus (megaesophagus)

Question 106

Large bowel: Intestinal segments at the end of their respective arterial supplies that are particularly susceptible to ischemic unjury.

The most at risk include the splenic flexure (SMA and IMA terminate) and rectosigmoid junction (IMA and hypogastric artery terminate).

Answer 106

“Watershed” zones

Question 107

Large bowel: Occurs as a result of a sudden, but transient reduction in blood flow. The predominant mechanism is non-occlusive ischemia.

Non-occlusive ischemia most often affects the “watershet” areas of the colon that have limited collateralization.

Answer 107

Colonic ischemia (Ischemic colitis)

• MC splenic flexure; rectosigmoid junction
• sudden onset of lack of blood flow – hypotension

Question 108

Large bowel: Factors that affect the severity of injury in ischemic colitis include:

1. Severity of vascular compromise
2. Time frame over which it develops

True/False - Severity of vascular compromise is based upon whether or not there is complete loss of perfusion (thrombus, embolus) or only partial loss (hypotension)

Answer 108

True

Question 109

Large bowel: Factors that affect the severity of injury in ischemic colitis include:

1. Severity of vascular compromise
2. Time frame over which it develops

The time frame is based on whether it is acute or chronic. _______ decreases in perfusion (e.g. thrombus) tend to cause transmural infarction, while _______ result in partial thickness (mucosal) infarctions.

Answer 109

1. Acute
   - -transmural
2. Chronic
   - -mucosal
   - -e.g. non-occlusive ischemia due to atherosclerosis of mesenteric arteries

Question 110

Large bowel: True/False - In ischemic colitis, the surface epithelium (superficial mucosa) is most susceptible to ischemic injury. This is because intestinal capillaries run from crypt to surface. This arrangement makes the surface epithelium the terminus of that particular vascular perfusion area.

Answer 110

True

*necrosis and sloughing of surface epithelial cells (while deeper layers of mucosa remain viable)

Question 111

Large bowel: A complication of Ischemic colitis that involves atherosclerotic narrowing of the mesenteric artery.

It most commonly occurs in elderly patients with severe post-prandial pain (LUQ), and results in weight loss due to lack of appetite and fear of pain after eating.

Answer 111

Mesenteric angina

**Classic case of Ischemic coliits: Patient who presents with bloody diarrhea after a AAA repair

Question 112

Large bowel: A patients presents with rapid onset of abdominal pain and tenderness along with bloody diarrhea.

History is significant for ischemic colitis and atrial fibrillation.

Answer 112

Infarct

• complication of ischemia colitis caused by vascular occlusion (obstructing embolus)
• Hx a-fib or vascular procedure
• fibrosis can lead to stricture – causes obstruction

Question 113

Large bowel: A 75 year old female presents with sudden onset of severe abdominal pain. She reports consistent desire to defecate and admits to passage of blood (or bloody diarrhea).

PSH: repair of AAA

Scope reveals well demarcated area of ischemic injury.

Answer 113

Ischemic colitis

**MC in older patients (>70y/o) and is frequently associated with coexisting cardiac or vascular disease (atherosclerosis).

Other causes: intense vasoconstriction secondary to the use of illicit drugs (cocaine).

*well demarcated area of ischemic injury

Question 114

Large bowel: Describes the pathologic entities of lymphocytic and collagenous colitis. Both entities are characterized by chronic non-bloody diarrhea with normal endoscopy.

Answer 114

Microscopic colitis

• differ histologically
• -Lymphocytic: lymphocytes; M = F
• -Collagenous: F > M

Question 115

Large bowel: Antibiotic-associated colitis is most often associated with overgrowth of what bacteria?

Answer 115

C. dificile

• anaerobic, gram +
• spore-forming, toxin-producing bacillus
• colonizes intestinal tract after normal gut flora disrupted

Question 116

Large bowel: Nearly any antibiotic can induce antibiotic-associated colitis. What are common etiologic agents? What is the MOA of C. diff?

Answer 116

Antibiotics:
–penicillins, fluoroquinolones, cephalosporins, clindamycin

MOA:
–exotoxins A and B (act on intestinal epithelial cells) cause tissue injury and diarrhea

Question 117

Large bowel:

1. Toxin _____ of C. diff induces inflammation by directly activating neutrophils. This leads to inc. intestinal fluid secretion and mucosal injury.
2. Toxin ____ is essential for the virulence of C. diff and is >10 x more potent than toxin A

Answer 117

1. Toxin A
   - -enterotoxin
   - -brush border
2. Toxin B
   - -cytotoxin
   - -pseudomembranes (yellow-green)
   - -actin depol

*Both toxins can promote neutrophil chemotaxis

Question 118

Large bowel: True/False - A minority of C. difficile strains that colonize the GI tract are non-toxinogenic and non-pathenogenic.

Answer 118

True

Question 119

Large bowel: Antibiotic associated colitis is most commonly a nosocomial infection acquired during hospitalization. C. difficile can survive as spores on objects and floors. It is not killed by alcohol based disinfectants (soap and water must be used.)

Risk of infection and severity can increase with age, and PPI’s (suppress gastric acid) also contribute to increased risk. What are methods of prevention?

Answer 119

1. prudent use of antibiotics
2. washing hands
3. routine use of gloves
4. isolation of infected patients
5. thorough cleaning of potentially contaminates surfaces

Question 120

Large bowel: A 64 year old patient complains of cramping abdominal pain, and profuse, watery/mucoid liquid stool. He had been admitted to the hospital 2 days ago and was prescribed antibiotics for treatment of bacterial pneumonia.

You suspect C. diff infection. How do you diagnose?

Answer 120

1. Liquid stool
   - -enzyme immunoassay for C. diff exotoxin A and/or B
   - -nucleic acid amplification test (NAATs) = detect genes that encode for toxins (rapid; high sensitivity and specificity; expensive)

Question 121

Large bowel: True/False - Toxic megacolon (and perforation) is a possible complication of C. diff infection (antibiotic induced colitis).

Answer 121

True

NOTE: B1/NAP1/O27 strain highly virulent

Question 122

Large bowel: A 64 year old patient complains of cramping abdominal pain, and profuse, watery/mucoid liquid stool. He had been admitted to the hospital 2 days ago and was prescribed antibiotics for treatment of bacterial pneumonia.

You confirm C. diff infection via enzyme immunoassay. How would you treat this patient?

Answer 122

1. Metronidazole, Vancomycin, Fidaxomicin
2. Surgical resection in resistant cases
3. Fecal microbial transplantation for recurrences

Question 123

Large bowel: Toxic megacolon is a potentially lethal complication associated with inflammatory processes of the colon (e.g. C. diff, IBD, ischemia). It is characterized by non-obstructive colonic dilatation plus systemic toxicity (fever, tachycardia, leukocytosis).

What is its cause?

Answer 123

–release of inflammatory mediators (NO) which inhibit SM tone leading to colonic dilation

• *early recognition and Tx imperative!!
• *inc. mortality w/ perforation

NOTE: history of ulcerative colitis and medication nonadherence who presents with bloody diarrhea, severe abdominal pain and distention, and signs of sepsis (fever, tachycardia, hypotension).

Question 124

Large bowel: Dilated, tortuous submucosal vessels that increase in incidence with age. It likely occurs from degeneration of the vascular walls.

Most common sites are cecum and ascending colon. Bleeding is episodic and self-limited.

Answer 124

Angiodysplasia

• bleeding = venous in origin
• less massive than diverticular bleed (arterial)

Question 125

Large bowel: True/False - Patients with angiodysplasia may have blood loss that can be overt, presenting with painless hematochezia or melena. More commonly though, bleeding is occult, with hemoccult (+) stools and Fe deficiency anemia.

Answer 125

True

*RLQ pain (think diverticulitis on the Right side)

Question 126

Large bowel: Angiodysplasia is thought to be due to intermittent, recurrent low grade obstruction of the submucosal veins of the colon. Over many years, the draining vessels become dilated.

Because these vessels are near the surface, bleeding may occur. In most patients, bleeding stops spontaneously. What are options for patients with recurrent bleeding?

Answer 126

1. Endoscopic cauterization
2. Intravascular embolization
3. Hemicolectomy

Question 127

Large bowel: Angiodysplasia is the MC vascular lesion of the GI tract (common cause of occult GI bleed.) It is associated with aortic stenosis, von Willebrand disease, and chronic kidney disease. It is believed that it may be secondary to coagulopathy in these patients.

How is it diagnosed?

Answer 127

Colonoscopy/angiography

Question 128

Large bowel: A sac-like protrusion of the colonic wall. It herniates (outpouches) into the mucosa and submucosa through the muscularis propria (rather than all 3 layers of the bowel wall.)

Answer 128

Colonic diverticula

• pseudodiverticuli (not all layers)
• MC sigmoid colon (high intraluminal pressure)
• inc. risk with age

Question 129

Large bowel: Colonic diverticula is due to increased intra-luminal pressure in combination with an area of weakness where the vasa recta penetrate the muscularis propria.

What are risk factors for developing diverticula of the colon?

Answer 129

1. Low fiber, high fat diet **
2. CT disorders
   - -Marfan, Ehlers Danlos

Question 130

Large bowel:

1. Divverticulum - single
2. Diverticula - plural
3. ______: the presence of one or more diverticula
4. ______: inflammation of one or more diverticula
5. ______: complications related to the presence of diverticula

Answer 130

3. Diverticulosis
4. Diverticulitis
5. Diverticular disease

Question 131

Large bowel: Most diverticula are asymptomatic and discovered incidentally on colonoscopy or imaging.

Potential complications include:

1. Bleeding
2. Diverticulitis

________ is due to exposure of the vasa recta to injury along its luminal aspect. It occurs in the absence of diverticulitis.

Answer 131

Diverticular bleeding

Question 132

Large bowel: True/False - As the diverticulum herniates, the penetrating vessels responsible for the wall weakness at that point becomes draped over the dome of the diverticulum, separated from the bowel lumen only by mucosa. These changes may result in segmental weakness of the artery, predisposing to rupture in the lumen.

Answer 132

True

Question 133

Large bowel: Inflammation of a diverticulum due to either a micro or a macroscopic perforation of the diverticulum. This is believed to occur from erosion of the diverticular wall by increased intraluminal pressure or inspissated food particles. Inflammation and focal necrosis ensue, resulting in perforation.

Answer 133

Diverticulitis

Question 134

Large bowel: Which of the following is a complication of diverticulitis?

a. formation of a localized abscess
b. fistula or obstruction
c. peritonitis
d. portal HTN

Answer 134

A-C

1. inflammation (mild) + small perforation (walled off by pericolic fat and mesentery)
2. formation of a localized abscess (or fistula/obstruction if adjacent organs involved)
3. poor containment of inflamed diverticulum or abscess = free perforation and peritonitis

Question 135

Large bowel: The following clinical findings best describe what large bowel syndrome?

1. Acute abdominal pain (LLQ) and fever
2. LLQ tenderness and mass
3. Leukocytosis

Answer 135

Diverticulitis

Question 136

Large bowel: How do you treat diverticular disease?

Answer 136

1. High fiber diet/fiber supplements
   - -prevent constipation = dec. pressure
2. antibiotics
   - -acute disease
3. colonic resection

Question 137

Large bowel: A functional disorder of the GI tract that is characterized by recurrent abdominal pain and altered bowel habits. It is common and occurs most often in females (late teen to 20s). Etiology is unknown.

Answer 137

Irritable bowel syndrome

Question 138

Large bowel: IBS patients often show evidence of visceral hypersensitivity and motility abnormalities.

What are common associations with IBS?

Answer 138

–Inc. anxiety and/or depression

*symptoms exacerbated by mental/physical stress = abnormal brain/gut interaction

Question 139

Large bowel: What is the diagnostic criteria for IBS?

Recurrent abdominal pain, on average, at least 1x per week in the last 3 months associated with > 2 of

a. related to defecation
b. associated with a change in frequency of stool
c. associated with a change in form (appearance) of stool
d. associated with bloody stool

Answer 139

A-C

Question 140

Large bowel: Colon polyps are discrete mass lesions that protrude into the intestinal lumen. The different types include:

1. Hyperplastic polyps
2. Jevenile (retention polyps)
3. Adenomatous polyp

____ is the MC type. It most often occurs in the left colon. It is small and benign with no risk of malignant change.

Answer 140

Hyperplastic polyp

Question 141

Large bowel: Colon polyps are discrete mass lesions that protrude into the intestinal lumen. The different types include:

1. Hyperplastic polyps
2. Jevenile (retention polyps)
3. Adenomatous polyp

________ are hamartomatous lesions that occur MC in the rectum in children. They are often benign and present with rectal bleeding. They may prolapse from the rectum.

Answer 141

Juvenile (retention) polyps

Question 142

Large bowel: Adenomatous polyps are dysplastic by definition and are thus premalignant. They include:

1. Tubular adenoma
2. Tubulovillous adenoma
3. Villous adenoma

The risk of malignancy is directly proportional to __

Answer 142

1. Size (>2cm)
2. Number
3. Villous component percentage
   - -Villous > tubulovillous > tubular

Question 143

Large bowel: _____ adenoma that is often larger than tubular adenomas and sessile. It has a higher risk of high-grade dysplasia (adenocarcinoma). It is named for its “finger-like” architecture

Answer 143

Villous adenoma

Question 144

Large bowel: True/Fasle - Inherited forms of cancer arise when one inherits a mutant allele of a particular tumor suppressor gene (e.g. APC).

This germline mutation is not sufficient on its own to initiate tumor development (because of the presence of a normal gene). However, if the normal allele becomes mutated, then tumor development is initiated.

Answer 144

True

*“head start” compared to sporadic - already have one mutated allele

Question 145

Large bowel: True/False - In sporadic (non-inherited) formes of cancer, all cells in the body begin with two normal copies of the tumor suppressor gene.

Thus, the cell must sequentially acquire mutations in both alleles of the tumor suppressor gene to initiate a tumor.

Answer 145

True

*require bi-allelic mutations of same tumor suppressor gene

Question 146

Large bowel: _____ is a rare, autosomal dominant disorder characterized by multiple hamartomatous polyps scattered throughout the GI tract (stomach to rectum), mucocutaneous hyperpigmentation, and increased risk of GI/non-GI cancers.

Answer 146

Peutz-Jeghers syndrome

• mucocutaneous hyperpigmenation (face, oral mucosa, lips, palms, genitalia)
• inc. risk malignancy (colon, pancreas, breast, lung, ovary, uterus)

Question 147

Large bowel: Peutz-Jeghers syndrome is due to a germline LOF mutation in _______, a serine/threonine kinase that is a negative regulator of mTOR signalling. It is a tumor suppressor, and thus, a key regulator of cancer cell metabolism and polarity.

Answer 147

STK11 (LKB1)

• symptoms appear 1st decade of life (beginning with hyperpigmentation of mouth)
• GI tract hamartomas start same age

Question 148

Large bowel: Autosomal dominant disorder characterized by innumerable adenomatous colorectal polyps. It is caused by a germline mutation in the adenomatous polyposis coli (APC) gene.

Answer 148

Familial denomatous polyposis

• at least 100 polyps must be present for Dx of FAP
• APC = negative regulator of WNT signalling

Question 149

Large bowel: APC regulates beta catenin levels by forming a “destruction complex” with other proteins. This helps to keep Beta-catenin levels low.

Binding of the WNT ligand to the extracellular WNT receptor sends a signal causing dissociation of this complex, enabling inc. levels of Beta-catenin. What happens to this free B-catenin?

Answer 149

1. B-catenin binds T-cell factor (TCF)
   - -translocation into nucleus – activate gene transcription
   - -unregulated cell growth

**Mutations in APC pre-present in most colon cancer (familial or spontaneous)

Question 150

Large bowel: A patient presents with a history of Familail adenomatous polyposis.

What would you expect to see on gross findings?

Answer 150

Gross:

• -polyps “carpet” the colon
• -minimum of 100 polyps (begin in mid-teens)

*inc. risk adenocarcinoma of SI (ampulla)

Question 151

Large bowel: The site of the APC mutation (FAP) affects the clinical phenotype. Some patients may develop fewer than 100 polyps (“attenuated FAP”) whereas others may have thousands.

How is FAP treated?

Answer 151

1. Colectomy
   - -early adulthood

*if left untreated = ALL develop colon cancer ~40y/o

Question 152

Large bowel: ________ refers to a constellation of inherited adenomatosis polyposis + additional manifestations. It is also due to a mutation in APC. Like FAP, the number of colonic polyps is related to the site of the mutation in the APC gene.

It commonly presents with benign extra-intestinal growths including:

1. Osteomas
2. Congenital hypertrophy of retinal pigment epithelium
3. Epidermal cysts
4. Fibromatosis

Answer 152

Gardner syndrome

• osteomas (benign; MC mandible and skull)
• Congential hypertophy (CHRPE)
• fibromatosis
• epidermal cysts

Question 153

Large bowel: True/False - Patients with Gardner syndrome have increased risk for extra-colonic malignancies including the duodenum, thyroid, pancreas, CNS and others.

Answer 153

True

*Turcot syndrome – familial colon cancer + brain tumors

Question 154

Large bowel: An uncommon, autosomal recessive polyposis syndrome.

It is due to bi-allelic mutations of the base-excision repair gene MUTYH. It is similar to attenuated FAP, but differs in inheritance pattern and gene mutation.

Answer 154

MUTYH-assocated polyposis

• polyps develop at later ages
• fewer than 100 adenomas
• ~50 y/o

Question 155

Large bowel: Hereditary non-polyposis colorectal cancer (Lynch Syndrome) is the most common syndromic form of colon cancer. It is caused by mutations in ________ genes that encode proteins responsible for the detection, excision, and repair of errors that occur during DNA replication.

Answer 155

*Mismatch repair genes

• MSH2 or MLH1 (MC genes)
• inherit one mutant + one normal allele

Question 156

Large bowel: In Hereditary non-polyposis colorectal cancer (HNPCC; Lynch Syndrome), patients have one normal allele and one inherited mutant allele. Loss of the second copy results in defects in mismatch repair and rapid accumulation of mutations.

What are the MC sites of these mutations?

Answer 156

short repeating sequences (microsatellites)

NUTSHELL: HNPCC is autosomal dominant due to mismatch repair defects. It is often asymptomatic but results in the development of adenomas that can rapidly progress to colorectal carcinoma (at a younger age than normal). Also have inc. risk other forms of cancer - endometrial, gastric, etc.

Question 157

Large bowel: Colon cancer in HNPCC tends to occur at a younder age (~44 y/o) in comparison to sporadic colon cancers.

They most often occur at which location?

Answer 157

Right colon

*inc. risk other cancer (esp. endometrial)

Question 158

Large bowel: Colon cancer may occur as a result of:

1. environmental factors
2. genetic factors
3. inflammatory factors

What are examples of environmental factors?

Answer 158

1. diets high in animal fat and calories **

2. cigarette smoke

Question 159

Large bowel: Colon cancer may occur as a result of:

1. environmental factors
2. genetic factors
3. inflammatory factors

What are genetic factors?

Answer 159

1. 1st degree relative w/ colorectal cancer
2. hereditary polyposis syndromes
   - -FAP = 100% risk
   - -HNPCC = 50-80% risk

Question 160

Large bowel: Colon cancer may occur as a result of:

1. environmental factors
2. genetic factors
3. inflammatory factors

True/False - Inflammatory factors include inflammatory bowel disease (esp. Ulcerative colitis) where risk increases with duration and extent of disease.

Answer 160

True

Question 161

Large bowel:

1. ______ sided cancers tend to present with signs of obstruction and changes in stool caliber (“pencil thin stool”).
2. _____ sided tumors tent to present with Fe deficiency anemia due to occult bleeding

Answer 161

1. Left sided
   - -sigmoid colon
2. Right sided
   - -right ascending colon

Question 162

Large bowel: Most sporadic cases of colon cancer follow the classic adenoma-carcinoma sequence. It involves progressive accumulation of multiple genetic mutations resulting in the transition from normal mucosa – low grade dysplasia – high grade dysplasia —- carcinoma.

Describe the sequence and mutations involved during the development of colorectal carcinoma

Answer 162

1. Normal colon
2. Mutation in APC
   - -early adenoma
3. activating K-RAS mutation
   –late adenoma
   (~50%)
4. loss of p53
   –carcinoma
   (~70-80%)

Question 163

Large bowel: True/False - Prostaglandin inhibitors may have a protective/preventive role in colorectal carcinoma because they inhibit prostaglandin-induced epithelial proliferation.

Answer 163

True

*NSAIDS/aspirin

Question 164

Large bowel: True/False - Mutations in APC is common in colorectal carcinoma and occurs early in the process. Loss of APC enables the accumulation of B-catenin, which promotes cell proliferation.

Furthermore, mutations in KRAS, SMAD2 and SMAD4 tumor suppressors, and TP53 tumor suppressor are common in colorectal carcinomas.

Answer 164

True

Question 165

Large bowel: K-Ras is a GTPase (converts GTP into its inactive form, GDP). A mutation in KRAS results in loss of the GTPase activity. What does this mean?

Answer 165

K-Ras remains bound to GTP (active form)

*continual cell growth

Question 166

Large bowel: Colorectal carcinoma is often asymptomatic and is detected during colonoscopy screening. If symptomatic, a patient often presents with non-specific findings (fatigue, weight loss) early in the disease.

Which of the following is a possible clinical presentation in advanced stages?

a. Fe deficiency anemia
b. Rectal bleeding
c. Abdominal pain
d. Change in bowel habits

Answer 166

All of the above

and:
- -intestinal obstruction/perforation (Left side)

NOTE: advanced disease (abdominal tenderness/mass; rectal bleeding; hepatomegaly; ascites)

Question 167

Large bowel: Screening for colorectal carcinoma should begin at the age of 50 unless other risk factors (e.g. IBD) are present. If a first degree relative has a Hx of CRC, begin screening 10 years prior to the age at which the relative’s cancer was diagnosed.

What are the most effective methods for screening?

Answer 167

1. Colonoscopy
   * gold standard
   - every 10 years
2. Guaiac-based fecal occult blood test (gFOBT)
   - -identifies Hb (turns guaiac reagent-impregnated paper blue due to peroxidase reaction)
3. CT colonography
4. Fecal immunochemical testing
   - -directly measures Hb in stool
5. Stool DNA testing
   - -test for mutations (colorectal neoplasia)

Question 168

Large bowel: Carcinoembryonic antigen (CEA) is a protein found in many types of cells, but is associated with tumors in adults. Why is it not recommended as a screening tool?

Answer 168

It is a tumor marker used to monitor for recurrence

~20ng/mL is strongly suggestive that cancer is still present

Question 169

Large bowel: Which of the following are features of Left-sided colorectal cancer?

a. bleeding complications
b. decreased stool diameter
c. abdominal cramping
d. obstruction/perforation possible

Answer 169

B-D

• stool is more formed; lumen is more narrow
• change in bowel habits

Question 170

Large bowel: A patient presents complaining of fatigue, feeling palpitations, decreased exercise tolerance and chest pain (angina). Labs reveal Fe deficiency anemia and “apple core” on gross examination.

You suspect

Answer 170

R. sided colorectal carcinoma

• colon larger and stool more liquid (dec. risk of obstruction)
• more likely to have bleeding complications (Fe anemia)
• Fe deficiency in >50y/o = colon cancer until ruled out

Question 171

Large bowel: True/False - Degree of differentiation of colorectal adenocarcinoma tends to correlate with the overall TNM stage.

Prognosis is related to the depth of tumor penetration into the bowel wall and presence/absence of metastasis (LN’s or distant).

Answer 171

True

*more poorly diff = more advanced

Question 172

Large bowel: Colon cancer metastasizes to the _____ lymph nodes and undergoes hematogenous disseminaction to the liver and other sites (lung, ovary, brain)

Answer 172

Mesenteric lymph nodes

• Lymph vessels carry tumor cells to regional LNs
• Veins of the colon carry tumor to liver* and other sites

Question 173

Large bowel: Treatment of colorectal carcinoma is surgical resection.

5-year survivial rate is inversely related to the stage of the cancer. If stage 1, there is a higher rate of survival compared to stage 5. What are the stages?

Answer 173

Stage O -

• -In situ
• -superficially involves mucosa

Stage 1:
–invades mucosa and submucosa

Stage 2:
–invades muscle layers, nearby tissues and organs

Stage 3:
–LN’s involved

Stage 4:
–distant spread

Question 174

Large bowel: With regard to colorectal carcinoma

1. Lef sided lesions tend to progress through the ____ pathway
2. Right sided lesions are more likely to arise through the ____ pathway.
3. S bovis endocarditis should always lead you to think

Answer 174

1. APC pathway
2. MSI (mismatch repair)
3. Colon cancer

Question 175

Large bowel: Inflammation of the appendix due to a blockage of the appendiceal orifice. This blockage leads to increased intraluminal pressure that, in turn compresses the blood supply leading to ischemia, bacterial growth and acute inflammation.

PMN’s can be seen in the muscularis layer.

Answer 175

Appendicitis

Kids: due to lymphoid hyperplasia (viral infection)
Adults: secondary to fecalith

Question 176

Large bowel: Clinical findings of acute appendicitis tend to occur in sequence.

What are these findings/symptoms?

Answer 176

1. Colicky periumbilical pain (MC)
2. Fever
3. Anorexia
   - –if not present, probably not appendicits
4. N/V
   - -pain precedes vomiting

Question 177

Large bowel:

1. Vomiting before onset of pain suggests ______
2. Vomiting after onset of pain suggests ____

Answer 177

1. gastroenteritis or obstruction

2. Appendicitis

Question 178

Large bowel: A patient presents to the hospital complaining of fever, anorexia and RLQ pain.

She is positive for McBurney’s test (b/w umbilicus and ASIS), and (+) Psoas sign (passive ext. of right hip). You also note rebound tenderness and guarding. What do you suspect? What do you expect to see on labs?

Answer 178

Acute appendicitis

-rebound/guarding = peritonitis

Labs:
–neutrophilic leukocytes

Question 179

Large bowel: Complications of acute appendicitis include:

1. post-op wound infections
2. perforation (periappendiceal abscess or peritonitis).

Aside from clinical observations and PE, what are methods for diagnosis acute appendicitis?

Answer 179

1. H and P
   - -must do pelvic in women (and B-HCG) to rule out gynecologic etiology
2. CT
   - -good sensitivity and specificity
3. Ultrasonography

Question 180

Large bowel: What are differential diagnoses that must be ruled out if you suspect acute appendicitis?

a. Viral gastroenteritis
b. Ovarian disorders
c. Ectopic pregnancy
d. Acute salpingitis
e. Diverticulitis

Answer 180

All of the above

–OVarian (cyst rupture, mittelshmerz)

Question 181

Large bowel: are due to elevated venous pressure within the hemorrhoidal plexus that are most often caused by straining during defecation. However, pregnancy (venous stasis) and portal HTN may also contribute to their development

Answer 181

Hemorrhoids

Question 182

Large bowel: Hemorrhoids are distinguished (internal vs. external) based on their relationship with the pectinate line.

Internal hemorrhoids occur above the pectinate line, and often present as painless. Blood on feces or toilet paper may be observed. What is the blood supply for internal hemorrhoids?

Answer 182

• Superior rectal vein – Inferior mesenteric vein – splenic vein – portal vein
• never assume that blood coating stool is an internal hemorrhoid. It may be colorectal or anal cancer

Question 183

Large bowel: Hemorrhoids are distinguished (internal vs. external) based on their relationship with the pectinate line.

External hemorrhoids arise below the pectinate line from the _______ vein. They are painful if thrombosed.

Answer 183

inferior rectal vein

Question 184

Large bowel: _____ refers to circuferential full-thickness protrusion of the rectal wall through the anus. It is believed to be due to chronic straining superimposed on pelvic floor relaxation. It is MC in older females.

Answer 184

Rectal prolapse

RF’s:

• -female, –inc. age, –multiparity, –history vaginal delivery, –prior pelvic surgery –chronic straining/constipation,
• -CF if children (2ndary to constipation)

Question 185

Large bowel: Glands surround the anal canal and release mucous into the canal to aid in defecation.

If a duct draining these glands becomes obstructed with stool, they can become infected and form an Anorectal abscess.

What are symptoms? How is it treated?

Answer 185

Symptoms

• -perianal pain/fever
• -difficulty voiding
• -fluctuant tender mass in perianal region

Tx:
–drainage

Question 186

Large bowel: An abnormal channel between the anorectal abscess and the anal mucosa or perianal skin

Answer 186

anal fistula

Question 187

Large bowel: A 55 year old male presents with complaints of severe, tearing pain during his bowel movements. He states he also has blood in the stool (mild hematochezia).

What do you suspect?

Answer 187

Anal fissure

• small, linear tear in anal mucosa (distal to pectinate line)
• trauma - passage of hard stool
• typically midline

Tx: stool softeners and dietary fiber

Question 188

Large bowel: ______ has hypertrophied anal papillae at the proximal end and a sentinel pile (skin tag) at the distal end.

Answer 188

Chronic anal fissure

Question 189

Environmental Exposure: Exogenous chemicals in the environment (air, water, food, soil) that can be absorbed into the body through inhalation, ingestion, and skin contact

Answer 189

Xenobiotics

*may be excreted, eliminated in expired air, or accumulate in bone, fat, brain

Question 190

Environmental exposure: Most solvents and drugs are _____, which facilitates their transport in the blood by lipoproteins and their penetration through the plasma membrane into cells

Answer 190

Lipophilic

Question 191

Environmental exposure: Most solvents, drugs and xenobiotics are metabolized to form inactive, water-soluble products (detox) OR are activated to form toxic metabolites.

Enzymes that catalyze the biotransformation of xenobiotics and drugs are known as

Answer 191

drug-metabolizing enzymes

Question 192

Environmental exposure: Detoxification by CYP 450 enzymes primarily occurs in the endoplasmic reticulum of the liver (though present in skin, lungs and GI).

Different CYPs have preferred substrate specificities, and reactions may produce ROS as byproducts. Which is an example of this?

a. toxic trichloromethyl free radical from carbon tetrachloride in the liver
b. DNA binding metabolites from benzo(a)pyrene carcinogen in cigarette smoke
c. acetic acid from acetaminophen breakdown

Answer 192

A and B

Question 193

Environmental exposure: True/False - CYPs are involved in the metabolism of a large number of commonly used drugs including acetaminophen, bariturates, warfarin, anti-convulsants. They also play a major role in alcohol metabolism.

Answer 193

True

Question 194

Environmental exposure: CYP activity varies amongst patients. This is most often due to exposure to drugs or chemicals that induce/diminish CYP activity. However, it may be a consequence of genetic polymorphisms in specific CYPs.

What are known CYP inducers?

a. environmental chemicals
b. drugs
c. smoking
d. hormones
e. ethanol

Answer 194

all of the above

1. Env.
   - -pesticides (chlorpyrifos, firpronil, permethrin, DEET)
2. Drugs
   - -phenytoin, rifampin, phenobarbital
3. Hormones
   - -estradiol

Question 195

Environmental exposure: CYP activity varies amongst patients. This is most often due to exposure to drugs or chemicals that induce/diminish CYP activity. However, it may be a consequence of genetic polymorphisms in specific CYPs.

What are known to decrease CYP activity?

a. fasting
b. starving
c. ketoconazole
d. grapefruit juice
e. lemons

Answer 195

A-D

*ketoconazole - blocks p450 dependent enzymes

Question 196

Environmental exposure: Although organophosphates are used mainly as pesticides and herbicides, they can also be used in petroleum additives, lubricants, antioxidants, flame retardants, and plastic modifiers.

Most cases of organophosphate toxicity result from exposure in an ____ setting. Absorption often occurs via skin, inhalation, and GI.

Answer 196

agricultural setting

• -mixing/spraying
• -workers returning prematurely to sprayed fields

Question 197

Environmental exposure: A patient presents with complaints of nausea, headache and muscle weakness. He reports symptoms several hours after arriving home from work.

On PE you note salivation, lacrimation and bronchospasm.

Occupation is in agriculture. You suspect

Answer 197

Organophosphate poisoning

MOA: Inhibit acetylcholinesterase (inc. acute cholinergic symptoms)

Question 198

Environmental exposure: What are symptoms of severe organophosphate poisoning?

a. bardycardia
b. tremors
c. chest pain
d. diarrhea

Answer 198

All of the above

–pumonary edema, cyanosis, convulsions, coma

*death may result from respiratory or heart failure

Question 199

Environmental exposure: Treatment for organophosphate poisoning involves a combination of Pralidozime and Atropine.

1. ______ accelerates reactivation of the inhibited Acetylcholinesterase
2. ______ counteracts the muscarinic effects (w/ no effect on nicotinic effect)

Answer 199

1. Pralidoxime
2. Atropine
   - -ventilatory support before administer atropine
   - -no effect on nicotinic (weakness/respiratory depression)

Question 200

Environmental exposure: Lead poisoning remains an important health hazard, particularly in children. Historically, major sources were house paints and gasoline. However, mining, foundries, car radiators, batteries and spray paint are other common sources (occupational hazards).

Low level lead poisoning can lead to subtle deficits in what functions?

Answer 200

• intellectual capacity
• behavioral
• hyperactivity
• poor organizational skills

*occupational: batteries, car exhaust, tin cans, pigments

Question 201

Environmental exposure: Lead is absorbed more readily in children than it is adults. Exposure may occur via contaminated air, food, water and/or surface contact.

What is the MOA of lead?

Answer 201

-binds sulfhydryl groups (toxic to multiple enzyme systems)

• interferes with calcium metabolism
• interferes with hematologic processes

Question 202

Environmental exposure: Lead interferes with heme synthesis by inhibiting the activity of what two enzymes?

Answer 202

1. delta-aminolevulinic acid dehydratase
2. ferrochelatase
   - -catalyzes incorporation of Fe into protoporphyrin
   - -inhibition causes an inc. in protoporphyrin (proximal)

**leads to basophilic stippling

Question 203

Environmental exposure: Lead can also cause GI, Skeletal, Neurologic and Renal symptoms. List examples of each.

Answer 203

1. GI
   - -“colic” - mimics acute abdomen
   - -abdominal pain/vomiting
   - -jaundice and black diarrhea
2. Skeletal
   - -lower bone mineral density
3. Neurologic
   - -protean symptoms

Question 204

Environmental exposure: True/False - Most absorbed lead is incorporated into bone and developing teeth, where it competes with calcium (half life 20-30 years).

However, the higher the intestinal absorption and more permeable the BBB of children is, the higher the susceptibility to brain damage.

Answer 204

True

Question 205

Environmental exposure: Lead poisoning can cause CNS disturbances in adults and children. However, peripheral neuropathies, such as peripheral demyelinating neuropathy, are predominant in which group?

Answer 205

adults

*neurotoxic effects due to inhibition of NT’s (from disruption of Ca2+ homeostasis)

Question 206

Environmental exposure: True/False - Lead interferes with the normal remodeling of cartilage and primary bone trabeculae in the epiphyses of children. It causes increased bone density detected as radiodense “lead lines”. These lead lines can also appear in the gums as a result of hyperpigmentation.

Answer 206

True

Question 207

Environmental exposure: Lead diagnosis is based upon clinical suspicion, especially with children. It often presents with

1. neurologic and behavioral changes
2. unexplained microcytic anemia
3. basophilic stippling on peripheral smear
4. ringed sideroblasts on marrow exam

Definitive diagnosis requires the detection of elevated blood levels of _____ and free _______

Answer 207

Elevated blood Lead and free red cell protoporphyrin

Question 208

Environmental exposure: This metal is most commonly associated with ingestion of contaminated fish (e.g. swordfish), and from vapors released from metallic mercury in dental amalgams (occupational hazard).

Answer 208

Mercury

1. natural degassing earth’s crust
2. industrial contamination – methyl mercury via bacteria
   * methyl mercury ingested by carnivorous fish (million-fold higher conc. than surrounding water)

Question 209

Environmental exposure: Mercury binds to _____ in certain proteins with high affinity, causing damage to the CNS and the kidney.

The developing brain is extremely sensitive to methyl mercury. Lipid solubility facilitates accumulation in the brain, which can cause neuromotor, cognitive and behavioral issues.

Answer 209

binds sulfhydryl groups

Question 210

Environmental exposure: Intracellular glutathione is the main protective mechanism against mercury-induced CNS and kidney damage.

What is its MOA?

Answer 210

Acts as sulfhydryl donor

Question 211

Environmental exposure: True/False - Inhalation of mercury vapor is most commonly associated with tremor, gingivitis and bizarre behavior.

Answer 211

True

Question 212

Environmental exposure: What groups should avoid consumption of fish known to contain high levels of mercury?

Answer 212

pregnant women

Question 213

Environmental exposure: Arsenic interferes with several aspects of cellular metabolism:

1. mitochondrial oxidative phosphorylation
2. enzymes and ion channels

What is its MOA in disturbing oxidative phosphorylation?

Answer 213

Trivalent arsenic can replace phosphates in ATP

Question 214

Environmental exposure: True/False: Arsenic is found naturally in soils and water. It is used in products such as wood preservers and herbicides. It is also present in Chinese and Indian herbal medicine.

Answer 214

True

NOTE: arsenic trioxide = frontline Tx for acute promyelocytic leukemia

Question 215

Environmental exposure: Arsenic most commonly affects GI, Nervous, Heart, Skin.

GI symptoms include vomiting, abdominal pain and diarrhea. What is a notable finding?

Answer 215

dark “black water” urine

Question 216

Environmental exposure: Arsenic most commonly affects GI, Nervous, Heart, Skin.

Neurologic effects usually occur 2-8 weeks after exposure, and consist of sensorimotor neuropathy that causes parasthesia, numbness and pain.

What are common skin changes associated with arsenic?

Answer 216

-hyperpigmentation and hyperkeratosis

Question 217

Environmental exposure: The most serious consequence of chronic exposure to arsenic is the increased risk for the development of

Answer 217

Cancers

• lungs, bladder
• skin
• non-sun exposed areas (palms/soles)

Question 218

Environmental exposure: Cadmium is an occupational and environmental pollutant that is preferentially toxic to the kidneys and the lungs through uncertain mechanisms.

Its MOA may involve increased production of ROS leading to obstructive lung disease (necrosed alveolar epithelial cells) and renal tubular damage.

What are sources of Cadmium?

Answer 218

• mining, electroplating
• nickel-cadmium batteries (disposed as household waste)
• soil and plant contaminant (directly through fertilizers or irrigation)
• *food

Question 219

Environmental exposure: Testing for heavy metal poisoning involves Whole blood and Urine.

Which is the preferred specimen for metabolic byproducts?

Answer 219

Urine

Question 220

Environmental exposure: Testing for heavy metal poisoning may include hair testing. It may be preferable for detection of RECENT exposure, and may serve as a marker for exposure to neurotoxic methymercury.

What are the pros and cons to use of hair?

Answer 220

Pros

• -easy to acquire
• -not a body fluid
• -may ID if supplementation of important minerals is needed

Cons

• -controversial
• -don’t know how to interpret (normal ranges not well established)

Requirements:

• -hair (0.25g) is minimum
• -1g preferred

Question 221

Trauma: A penetrating wound involves solid understanding of the anatomic relationships.

True/False - In the case of a penetrating projectile that is still in place (knife wound), it is best removed in a surgical setting.

Answer 221

True

Question 222

Trauma: Blunt force trauma is a common cause of death in accidents of all types.

Examples include:

1. seat belt sign
2. splenic rupture/laceration
3. diaphragm injury
4. pancreas injury
5. IVC injury

_______ is a contusion or abrasion on the abdomen of a restrained occupant involved in a motor vehicle crash. It often involves injury to the abdominal organs or spine.

Answer 222

Seat belt sign

**get abdominal CT ** (if abnormal findings - surgical consultation)

• energy diverted from head to chest and abdomen
• relative risk of small bowel injury is x4.7 w/ seatbelt sign

Question 223

Trauma: Splenic rupture is often caused by blunt abdominal trauma and may result in intraperitoneal hemorrhage requiring emergent splenectomy.

What are etiologies of “spontaneous” splenic rupture?

Answer 223

1. Infectious mononucleosis (EBV)
2. Myeloproliferative neoplasm
3. Malaria or typhoid fever

*thin individuals = degree of trauma may be minor and go unnoticed

Question 224

Trauma: True/False - Chronically enlraged spleens are unlikey to rupture due to the effect of extensive reactive fibrosis

Answer 224

True

Question 225

Trauma: Diaphragmatic injury is relatively uncommon but accounts for 3% of abdominal injuries. Penetrating occurs more often than blunt injuries.

Which side of the diaphragm is most often affected?

Answer 225

Left - 75%
Right - 23%
Bilateral - 2%

Question 226

Trauma: Blunt trauma to the diaphragm can result in sudden transfer of pressure gradients. Altered pressure gradients can lead to what complications?

Answer 226

1. direct injury
2. herniate abdominal contents
3. repiratory and hemodynamic abnormalities

Question 227

Trauma: Injury to the diaphragm can be difficult to repair, and morbidity of missed injury is high.

Imaging has relatively low sensitivity. What can be used to diagnose diaphragm injury?

Answer 227

1. high index of suspicion
2. laparoscopy/thoracosopy
3. CT w/ oral contrast

Question 228

Trauma: True/False - IVC injury is relatively uncommon, but may cause hemoperitoneum and vascular instability in a trauma patient

Answer 228

True

Question 229

Trauma: The pancreas lies in a relatively protected position high in the retroperitoneym. It is less commonly injured by blunt trauma (compared to liver and spleen). Most frequently, injuries involve penetrating abdominal trauma.

What are features of pancreatic injury noted on PE?

Answer 229

1. seat belt marks
2. “handle bar” history/markings
3. flank ecchymoses
4. dull epigastric or back pain
5. peritoneal irritation

*contained fracture of the spleen w/ retroperitoneal hematoma or leak

Question 230

Trauma: Pancreas injury is associated with additional threatening injuries. How is it diagnosed?

Answer 230

1. plasma amylase/lipase levels
2. CT
3. MRCP/ERCP
4. Exploratory laparotomy

Question 231

Foreign bodies: Once in the stomach, 95% of all ingested objects pass without difficulty through the remainder of the GI tract. Perforation after ingestion of a foreign body is <1%.

Where is perforation more likely to occur?

a. areas of physiologic sphincters
b. acute angulation
c. congenital gut malformations
d. areas of previous bowel surgery
e. branching of the abdominal aorta to common iliac

Answer 231

A-D

a. areas of physiologic sphincters
- (pylorus, ileocecal valve

b. acute angulation
- -duodenal sweep

c. congenital gut malformations
- -web, diverticula, diaphragm

d. areas of previous bowel surgery
- -adhesions, fibrosis

Question 232

Foreign bodies: Hx is the best way to determine the presence of a foreign body. They most commonly occur b/t the ages of 6 mos and 6yrs.

Approximately 90% of foreign bodies are opaque, and radiologic exam is routinely performed to ID the type, number and location. What are the MC objects in kids? adults?

Answer 232

Kids:
–coins (ingested)

Adults:

• -meat or food impactions
• -accidental

Question 233

Foreign bodies: True/False - contrast radiographs may be necessary to ID some objects such as plastic parts or toys

Answer 233

True

Question 234

Foreign bodies: Conservative management is indicated for most foreign bodies that have passed through the esophagus and entered the stomach. Most objects pass through the intestine within a week.

While waiting, recommend the patient:

1. continue a regular diet
2. observe stools for the appearance of the ingested object.
3. Avoid cathartics

What should be suspected if the object fails to pass within 3-4 weeks?

Answer 234

–congenital malformation or acquired bowel abnormality

Question 235

Foreign bodies: Certain objects pose more risk than others such as sharp foreign bodies (straight pins) and magnets. If a patient ingest a sharp foreign body, weekly assessments are required.

How does this compare to ingestion of magnets?

Answer 235

1. Magnets = bowel perforation
   - -If in esophagus = immediate removal
   * batteries too

*multiple magnets – lead to pressure necrosis and perforation

Question 236

Foreign bodies: Imaging is commonly used to ID foreign bodies (unless otherwise contraindicated).

Foreign bodies appear ____ on imaging

Answer 236

opaque

Question 237

Cirrhosis: Cirrhosis is a widespread liver dysfunction characterized by widespread fibrosis. Common causes of cirrhosis include:

1. Chronic viral hepatitis (B, C)
2. Alcoholic liver disease
3. Hemochromatosis
4. Non-alcoholic fatty liver

Alcohol consumption is a common cause of liver disease. The quantity and duration of alcohol intake are important factors influencing the severity of disease. How is alcohol metabolized (by the liver)?

Answer 237

via Alcohol dehydrogenase pathway (MC)

1. Ethanol — Acetaldehyde (toxic byproduct)
   –cytoplasm
   –alcohol dehydrogenase
   (NAD – NADH)
2. Acetaldehyde – Acetate
   –mitochondria
   –aldehyde dehydrogenase
   (NAD –NADH)

Question 238

Cirrhosis: The first manifestations of alcoholic liver injury are fatty changes (fat deposition in hepatocytes) and perivenular fibrosis. This is better known as

Answer 238

Steatosis

*reversible if quit drinking OH

Question 239

Cirrhosis: Hepatitis may be caused by severe exposure to OH, and may occur in combination with steatosis. What are the features of hepatitis?

Answer 239

Liver cell necrosis
Inflammation
Mallory bodies
Fatty change

Question 240

Cirrhosis: Cirrhosis is the final endpoint of hepatic damage. It is characterized by fibrosis and hyperplastic nodules. It can occur from continued exposure to OH, and repeated attacks of Hepatitis.

What are risk factors for developing alcoholic liver disease?

Answer 240

1. Quantity/Duration of alcohol intake
   – >2 drinks/day men
   — > 1 drink/day women
   (many years)
2. Gender
   - -women more susceptible
3. Concurrent HCV infection
   - -inc. risk cirrhosis and hepatocell. carcinoma
   * *AVOID OH

Question 241

Cirrhosis: The major pathway of ethanol metabolism is conversion to acetaldehyde by alcohol dehydrogenase, and subsequent conversion to acetate via acetaldehyde dehydrogenase.

What are the minor pathways?

Answer 241

1. Microsomal enzyme oxidation system
   - -CYP 450
   - -form acetaldehyde

NOTE: CYP 2E1 is inducible

• -tolerance in chronic alcoholics
• chronic OH inc. risk of acetaminophen toxicity (CYP 2E1 forms toxic metabolite)

Question 242

Cirrhosis: Some Asians have a relative deficiency of acetaldehyde dehydrogenase (ALDH2) isoform and are thus less able to metabolize alcohol. As a result, acetaldehyde accumulates in the body and results in

Answer 242

Alcohol flush reaction

Question 243

Cirrhosis: Oxidation of ethanol requires conversion of NAD+ to its reduced form NADH. Because NAD+ is required for the oxidation of fat, its depletion inhibits fatty acid oxidation, resulting in accumulation of fat within hepatocytes (i.e. steatosis).

True/False: Fat accumulation within hepatocytes may occur within days of EtOH ingestion, however, with abstinence, the normal redox state is restored, the lipid is mobilized, and steatosis resolves.

Answer 243

True

Question 244

Cirrhosis: Steatosis (accumulation of fat within hepatocytes) is the initial and most common histologic response to alcohol. It is often asymptomatic, although a large, tender liver may be present.

With continued drinking, some patients may progress to “alcoholic hepatitis”. What are the histologic features of hepatitis?

Answer 244

• hepatocyte damage
• neutrophilic inflammation
• perivenular/sinusoidal fibrosis

*reversible w/ cessation

Question 245

Cirrhosis: Although it is not clear why some develop hepatitis, it is thought to be due to cytokines, oxidative stress and toxic metabolic products of alcohol.

What are some of the cyokines involved?

Answer 245

1. Neutrophil-attracting
   - -IL-8
2. Non-neutrophil attracting
   - -IL-1, IL-6, TNF

NOTE: minor metabolic pathways (activated by heavy drinking) can produce ROS and cause hepatitis

Question 246

Cirrhosis: A patient presents complaining of feeling unwell. He states he has had a fever for the past 4 hours, and has no appetite. On PE, you note yellow discoloration of his skin and eyes (jaundice) and upon palpation of his abdomen, note he has tender hepatomegaly. You suspect alcoholic hepatitis due to his history of drinking excessive alcohol.

Histology reveals:

• -neutrophilic inflammation
• -fibrosis (perivenular/sinusoidal)
• -Mallory-Denk bodies

What would you expect to see on labs?

Answer 246

Histo:
-Mallory-Denk bodies
(damaged cytokeratin IF’s; suggest OH-induced liver injury)

Labs: 
--mod. elevation of AST and ALT (<300)
(AST:ALT ratio >2)
--inc. serum bilirubin
--inc. gamma-glutamyl transferase (GGT)
--leukocytosis w/ neutrophils mostly

Question 247

Cirrhosis: True/False - Patients with more serious liver disease may present with hypoalbuminemia and prolonged PT (elevated INR)

Answer 247

True

Question 248

Cirrhosis:

1. Alanine aminotransferase (ALT) is found primarily in the _______.
2. Aspartate aminotransferase (AST) is found both in the cytoplasm as well as within the _________.

Alcohol causes mitochondrial injury, thus causing a disproportionate increase in AST > ALT.

Answer 248

1. ALT - cytoplasm
2. AST - cytoplasm and mitochondria

*NO lab test differentiates alcoholic liver disease from other causes of liver disease, but AST to ALT ratio >2 is highly suggestive!

Question 249

CIrrhosis: Diffuse hepatic fibrosis with the replacement of normal liver architecture by regenerative nodules.

Early disease may be at least partially reversible with treatment of the underlying cause (e.g. if alcohol, abstinence)

Answer 249

Cirrhosis

MC causes:

• Hep C
• OH liver disease
• non-OH liver disease

NOTE: rate of progression of chronic liver disease to cirrhosis varies based on underlying etiology

Question 250

Cirrhosis: Pathologic features of cirrhosis consist of development of fibrosis to the point of architectural distortion + formation of regenerative nodules.

This results in:

a. decreased hepatocellular mass and function
b. hepatitis
c. inc. risk perforation
d. altered blood flow through the liver

Answer 250

A and D

• dec. mass, function
• altered blood flow

Question 251

Cirrhosis: Cirrhosis occurs when hepatocyte damage causes activation of hepatic stellate cells (myofibroblasts).

These cells become fibrogenic, increasing deposition of collagen fibers. With progression, the fibrous tissue compresses the vasculature and impairs blood flow through the liver. What happens when the liver tries to repair itself?

Answer 251

-formation of nodules of regenerating hepatocytes surrounded by fibrosis (a.k.a. cirrhosis)

• TGF-B – potent fibrogenic cytokine
• Hepatic stellate cell (Ito) cells normally stores Vitamin A

Question 252

Cirrhosis:

1. Normally, blood from the upper body and esophagus drains into the SVC.
2. Blood from the inferior esophagus drains through the left gastric vein into the portal vein.
3. Blood from spleen (via splenic vein) and gut (mesenteric veins) also drain into the portal vein.
4. The portal vein flows into the liver.

What happens in the case of cirrhosis?

Answer 252

1. Diffuse fibrous tissue throughout liver impairs blood flow
2. Blood backs up into the spleen (splenomegaly)
3. Backs up into the L. gastric vein
   - -dilated submucosal veins (lower esophagus )
   - -esophageal varices
4. Backs up into IMV
   - -caput medusa

Question 253

Cirrhosis: The development of dilated collateral vessels as blood flows through paraumbilical veins.

This is due to increased portal venous pressure that opens pre-existing vascular channels and causes blood to be diverted from the portal systemic circulation.

Answer 253

Caput medusae

esophageal varices can also occur

Question 254

Cirrhosis: Which of the following is a clinical manifestation of portal hypertension caused by cirrhosis?

a. splenomegaly (hypersplenism)
b. gastroesophageal varices
c. para-umbilical venous collaterals
d. asciteies

Answer 254

all of the above

1. splenomegaly
   - -cyopenias (thrombocytopenia)
2. varices
   - -high risk perforation, bleeding
   - -inc. mortality
3. venous collaterals
   - -caput medusae

Question 255

CIrrhosis: Cirrhosis can lead to impaired hepatic function, including

1. decreased protein synthesis
2. altered metabolism of sex hormones

Dec. protein synthesis can lead to dec. clotting factors and thus increased bleeding and prolonged PT. Furthermore, decreased synthesis of albumin can lead to edema and/or ascites due to loss of

Answer 255

oncotic pressure

Question 256

CIrrhosis: Cirrhosis can lead to impaired hepatic function, including

1. decreased protein synthesis
2. altered metabolism of sex hormones

Metabolism of estrogen is impaired leading to elevated estrogen. Increased estrogen leads to increased sex hormone-binding globulin (SHBG). What is the consequence of inc. SHBG?

Answer 256

1. Inc. SHBG = Inc. bound testosterone
   - -less free testosterone (active form)
   - -hypogonadism

Symptoms/Clinical:

• -decreased libido
• -ED
• -palmar erythema
• -gynecomastia
• -testicular atrophy

Question 257

Cirrhosis: A clinical manifestations of cirrhosis caused by altered sex hormone metabolism. It is characterized as an exaggeration of normal speckled mottling of palm

Answer 257

Palmar erythema

*spider angioma also a clinical manifestation

Question 258

Cirrhosis: Ascites is caused by a combination of:

1. fibrosis of the liver that disrupts normal hepatic architecture
2. hypoalbuminemia

Fibrosis contributes to ascites by increasing resistance to flow through the liver, and increasing portal venous pressure. What does this lead to?

Answer 258

-increased hydrostatic pressure within the portal vein

Question 259

Cirrhosis: Ascites is caused by a combination of:

1. fibrosis of the liver that disrupts normal hepatic architecture
2. hypoalbuminemia

Decreased hepatic protein synthesis (albumin) leads to decreased oncotic pressure. This, with increased fibrosis and hydrostatic pressure, leads to extravasation of fluid into the peritoneal cavity. How does this ultimately lead to ascites?

Answer 259

1. loss of fluid in the peritoneum = dec. intravascular volume
2. activation of RAAS
3. Inc. aldosterone = inc. fluid retention
   - -inc. hyrostatic pressure
   - -inc. ascites

Question 260

Cirrhosis: Analysis of the peritoneal fluid can help to determine etiology of ascites. This is done by Serum-ascites albumin gradient.

How does the Serum-ascites albumin gradient distinguish between etiologies?

Answer 260

1. Serum albumin-peritoneal fluid albumin > 1.1 g/dL
   - -portal HTN/cirrhosis
2. Serum albumin-peritoneal fluid albumin < 1.1 g/dL
   - -another cause (peritoneal inflammation/tumor)

NOTE: ascites due to portal HTN has dec. albumin and thus inc. gradient

Question 261

Cirrhosis: On physical exam, ascites appears with abdominal distension, fluid wave and shifting dullness.

It can be ID’d by serum-ascites albumin gradient, and cell count. Other testing (amylase, lipase) may be performed based on the clinical scenario.

How is it treated?

Answer 261

Paracentesis

NOTE: Cell count and differential: Inc. WBC’s (PMN’s) suggests bacterial peritonitis

Question 262

Cirrhosis: The peritoneal fluid in a cirrhotic patient is prone to becoming infected (spontaneous bacterial peritonitis).

It is believed to be 2ndary to overgrowth of an intestinal organism followed by translocation of that organism to the mesenteric lymph nodes and then peritoneal fluids.

What are common organisms associated with bacterial peritonitis?

Answer 262

E. coli and Klebsiella pneumonia

NOTE: ascites w/ low protein content (e.g. cirrhosis) is particularly susceptible to SBP due to less anti-microbial (opsonic) activity

Question 263

Cirrhosis: “Spontaneous” bacterial peritonitis should be suspected when the peritoneal fluid shows what?

Answer 263

1. Inc. WBC count
   - - >50% neutrophils
2. Culture is (+)
3. 2ndary causes of peritonitis are excluded

Question 264

Cirrhosis: Hepatorenal syndrome is described as renal failure secondary to liver failure when there is nothing intrinsically wrong with the kidneys.

It is caused by release of vasodilators (e.g. NO) triggered by portal hypertension. Vasodilation results in decreased effective arterial blood volume which leads to inc. RAAS and sympathetic outflow.

What are manifestations of hepatorenal syndrome?

Answer 264

1. Dec. urine output

2. Inc. BUN and serum Cr

Question 265

Cirrhosis: A reversible syndrome of impaired brain function that occurs in patients with advanced liver failure.

It involves changes in behavior and personality, changes in sleep-wake cycle, confusion and coma. The mechanisms that cause the brain dysfunction are still unknown (ammonia contributes).

Answer 265

Hepatic encephalopathy

Tx: removal of precipitating event and excess ammonia

Question 266

Cirrhosis: Ammonia is a neurotoxin that interferes with brain function. It is produced from nitrogenous sources (e.g. glutamine), a component of dietary protein. Glutamine gets converted to ammonia by enterocytes and by colonic bacterial catabolism.

In the normally functioning liver, ammonia is almost completely cleared. Impaired liver fxn and shunting of blood leads to increased levels of ammonia. What can help reduce these levels?

Answer 266

1. Dietary protein restriction

2. Lactulose – dec. absorption of ammonia from GI tract

Question 267

Cirrhosis: Which of the following is a clinical manifestation of hepatic encephalopathy?

a. changes in sleep pattern
b. altered attention span
c. loss of cognitive abilities
d. asterixis, slurred speech

Answer 267

all of the above

1. Altered consciousness
   - -changes in sleep; lethargy, stupor, coma
2. Altered cognition
   - -attention span; loss of cognitive ability
3. Personality/Behavior
   - -euphoria, dec. inhibitions
   - -inappropriate/bizarre behavior
4. Neuromuscular
   - -asterixis (“flapping wrists”), slurred speech, ataxia

Question 268

Cirrhosis: Bilateral, asynchronous flapping motions of the outstretched, dorsiflexed hands. MC seen in those with hepatic encephalopathy

Answer 268

Asterixis

*brief rapid relaxation of dorsiflexion of the wrist = flap

Question 269

Cirrhosis: Pungent smell to the breath caused by increased concentration of dimethyl sulfide

Answer 269

Fetor hepaticus

Question 270

Cirrhosis: An autosomal recessive disorder characterized by skin hyperpigmentation due to iron and melanin deposition.

It is the MC genetic disorder in Northern European ancestry. It is usually diagnosed in males by the 5th decade, and diagnosed later in women due to the protective effects of menstrual blood loss.

Answer 270

Hereditary hemochromatosis

• mutation in HFE gene = dec. hepcidin synthesis
• unregulated absorption of dietary iron (iron overload)
• bronze color of skin = inc. in sun-exposed areas

Question 271

CIrrhosis: Hereditary hemochromatosis is due to a mutation in the hereditary hemochromatosis (HFE) gene that results in iron overload and hyperpigmentation of the skin.

Mechanisms of iron toxicity include:

1. Lipid peroxidation
2. DNA injury
3. Activation of hepatic stellate cells

_____ stimulates collagen deposition. CIrrhosis is a major finding in advanced disease.

Answer 271

Activation of hepatic stellate cells

Question 272

CIrrhosis: Hereditary hemochromatosis is due to a mutation in the hereditary hemochromatosis (HFE) gene that results in iron overload and hyperpigmentation of the skin (bronze color).

Mechanisms of iron toxicity include:

1. Lipid peroxidation
2. DNA injury
3. Activation of hepatic stellate cells

_____ involves breakdown of lipids within cell membranes via Fe-catalyzed free radical reactions. This leads to cell injury

Answer 272

Lipid peroxidation

Question 273

CIrrhosis: Hereditary hemochromatosis is due to a mutation in the hereditary hemochromatosis (HFE) gene that results in iron overload and hyperpigmentation of the skin (bronze color).

Mechanisms of iron toxicity include:

1. Lipid peroxidation
2. DNA injury
3. Activation of hepatic stellate cells

____ occurs from Fe-induced reactive O2 species

Answer 273

DNA injury

Question 274

CIrrhosis: Hereditary hemochromatosis results from iron being deposited in the tissues. Iron is hepatotoxic and thus increases the risk for development of cirrhosis as well as hepatic cell carcinoma.

What are other manifestations of hereditary hemochromatosis?

Answer 274

1. Pancreas
   - -B islet cell damage
   - -Inc. risk DM
2. Heart
   - -dilated cardiomyopathy
   - -conduction issues
3. Pituitary
   - -dec. trophic hormones (dec. testosterone)
   - -inc. risk hypothryoidism, hypogonadism
4. Joints
   - -synovial involvement = arthropathy

Question 275

Cirrhosis: In early stages of Hereditary hemochromatosis, patients are asymptomatic. It is often discovered by abnormal labs.

What are methods for screening and confirming HH?

If treated, life expectancy is normal. How is it treated?

Answer 275

Screening:
-Transferrin saturation (>45% = further eval)

Confirmation:

• Genetic testing
• -Liver biopsy (quantitative iron)

Tx:

• -regular phlebotomy (depletes tissue iron stores)
• -Fe chelation therapy

Question 276

CIrrhosis: Acquired hemochromatosis (iron overload) is usually secondary to iron acquired via recurrent RBC transfusions.

Each unit of packed RBCs contains 200-250mg of iron. In whom would this typically occur?

Answer 276

-chronic hemolytic disorders (sickle cell; B-thalassemia major)

Question 277

CIrrhosis: Less common causes of cirrhosis include:

1. Wilson disease
2. Alpha-1-anti-trypsin deficiency
3. Primary biliary cholangitis (cirrhosis)
4. Secondary biliary cirrhosis

_____ is an AR disorder of copper metabolism. It is caused by a mutation in the ATP7B gene and affects males and females equally.

Answer 277

Wilson Disease

–ATP7B encodes for hepatic Cu transport protein

Question 278

CIrrhosis: Normally, Cu is incorporated by the liver into ceruloplasmin which is secreted into the plasma. In Wilson’s disease, this process is impaired due to the loss of the Cu transport protein (ATP7B mutation).

This results in diminished excretion of copper through the bile. Instead, Cu accumulates within tissues (oxidative injury). What are clinical manifestations?

a. Wing beating tremor
b. Kayser Fleisher ring
c. Acute hepatitis
d. Fanconi syndrome

Answer 278

All of the above

*most diagnosed in childhood - young adulthood

1. Liver dysfunction
   - -acute hepatitis/liver failure to chronic hep/cirrhosis
2. Neurologic
   - -similar to Parkinson, Wing beating tremor
   - -psychiatric (depression, phobias, mood changes)
3. Kayser-Fleisher ring
   –Cu deposits in Descemet’s membrane of cornea
   (limbus junction of sclera/cornea)
4. Fanconi syndrome
   - -dec. PT reabsorption of ions, water, electrolytes
   - -inc. excretion of all of these things

*NUTSHELL: Suspect in cases non-specific liver diseasde and non-specific extrapyramidal symptoms before age 35

Question 279

Cirrhosis: Wilson disease can be diagnosed via:

1. Increased hepatic copper
2. Increased urinary copper
3. Low serum ceruloplasmin
4. Decreased total serum copper

How is it Tx?

Answer 279

Tx:
–Cu chelating agents (D-penicillamine)

Dx:

• -Liver biopsy is diagnostic (inc. hepatic Cu)
• -Inc. urinary: free Cu in blood excreted by kidneys

Question 280

CIrrhosis: Less common causes of cirrhosis include:

1. Wilson disease
2. Alpha-1-anti-trypsin (AAT) deficiency
3. Primary biliary cholangitis (cirrhosis)
4. Secondary biliary cirrhosis

_____ is a protease inhibitor produced by hepatocytes. It acts to neutralize neutrophil-derived proteases (trypsin, elastase). Lack of this inhibitor results in unopposed neutrophil elastase activity leading to digestion of elastin and collagen in the alveolar walls of the lungs.

Answer 280

Alpha-1 anti-trypsin

–proteases released in lungs due to exposure to pathogens – AAT prevents unregulated protease activity

–abnormal AAT is not released from hepatocytes (low serum and alveolar AAT levels)

Question 281

Cirrhosis: True/False - Unregulated protease activity due to AAT deficiency results in septal loss and panacinar emphysema

Answer 281

true

Question 282

Cirrhosis: In AAT deficiency, expression of alleles is co-dominant.

1. M = normal allele (MM = normal genotype)
2. S and Z = deficient variants (ZZ = most severe)

Abnormal variant of AAT polymerizes and accumulates within hepatocytes. This can present as neonatal hepatitis and cirrhosis (MCC of cirrhosis in children). How does it appear on histology?

Answer 282

PAS (+) inclusion in the periportal hepatocytes

Question 283

CIrrhosis: Less common causes of cirrhosis include:

1. Wilson disease
2. Alpha-1-anti-trypsin (AAT) deficiency
3. Primary biliary cholangitis (cirrhosis)
4. Secondary biliary cirrhosis

_____ results from autoimmune destruction of intra-hepatic bile ductules. It is more common in females than males and usually occurs in middle age.

Answer 283

Primary biliary cholangitis

Question 284

Cirrhosis: A patient presents complaining of fatigue and vague RUQ discomfort. You note pruritus on PE.

Her labs indicate:

1. Inc. alkaline phosphatase (ALP)
2. Inc. y-glutamyl transpeptidase (GGT)
3. Inc. IgM

You suspect

Answer 284

Primary biliary cholangitis

1. Inc. serum IgM and circulating autoabs (anti-mitochondrial) **
2. Granulomatous inflammation (liver)
3. T-cell infiltrate within biopsy (destruction of intra-hepatic bile ducts)

• fatigue - pro-inflamm cytokines
• other autoimmune med. disease

Question 285

CIrrhosis: Primary biliary cholangitis may progress to cirrhosis and poses an inc. risk of hepatocellular carcinoma.

What would you expect to see (labs) once cirrhosis develops?

Answer 285

1. Inc. bilirubin
2. Prolonged PT
3. Dec. albumin
4. Thrombocytopenia (portal HTN splenomegaly)

Question 286

Cirrhosis: What is the diagnostic hallmark of primary biliary cholangitis?

Answer 286

Anti-mitochondrial antibodies in serum

*most react against E2 subunit of pyruvate dehydrogenase

Question 287

Cirrhosis: Cirrhosis that develops secondary to chronic obstruction of the extra-hepatic biliary tract.

Answer 287

Secondary biliary cirrhosis

Question 288

Neoplasms: The most common liver tumor is due to metastasis from another site. However, there are a variety of benign and malignant tumors of the liver. Benign tumors include:

1. Focal nodular hyperplasia
2. Hepatic adenoma
3. Hemangioma

________ is a benign neoplasm of hepatocytes that predominates in young adult women (20s-40s). It is strongly associated with the use of oral contraceptives (possibly due to stimulation of steroid receptors on hepatocytes). It may also be associated with use of anabolic androgens in body builders.

Answer 288

Hepatic adenoma

*regress w/ discontinuation of OCPs/androgens

Labs:
–normal AFP

Complications:

• -bleeding
• -malignant transformation (in hepatocell. carcinoma)

Question 289

Neoplasms: The most common liver tumor is due to metastasis from another site. However, there are a variety of benign and malignant tumors of the liver. Benign tumors include:

1. Focal nodular hyperplasia
2. Hepatic adenoma
3. Hemangioma

____ is a benign tumor-like condition of unknown etiology. It usually arises in young to middle aged adults and is more common in women. It is characteristically small with a central stellate scar.

Answer 289

Focal nodular hyperplasia

*asymptomatic w/ no risk of malignant transformation

Question 290

Neoplasms: The most common liver tumor is due to metastasis from another site. However, there are a variety of benign and malignant tumors of the liver. Benign tumors include:

1. Focal nodular hyperplasia
2. Hepatic adenoma
3. Hemangioma

_____ is a benign tumor of endothelial cells (MC benign mesenchymal hepatic tumor). It is typically asymptomatic and is often discovered incidentally. It is most common in females 30-50 years of age. Biopsy is contraindicated due to inc. risk of hemorrhage.

Answer 290

Hemangioma

*highly vascular (large diameter of vascular channels)

Question 291

Neoplasms: The most common liver tumor is due to metastasis from another site. However, there are a variety of benign and malignant tumors of the liver. Malignant tumors include:

1. Hepatocellular carcinoma (HCC)
2. Cholangiocarcinoma
3. Angiosarcoma
4. Hepatoblastoma

A rare, high grade neoplasm of endothelial cells. It is the MC sarcoma arising in the liver. It is often seen in older males. Risk factors include exposure to vinyl chloride, arsenic and anabolic steroids.

Answer 291

Angiosarcoma

Clinical:

• -abdominal pain, fatigue, weight loss
• -jaundice
• -liver failure, possible rupture w/ intra-abdominal bleed (death)
• -metastasis common (lungs, bone, adrenals)

Question 292

Neoplasms: The most common liver tumor is due to metastasis from another site. However, there are a variety of benign and malignant tumors of the liver. Malignant tumors include:

1. Hepatocellular carcinoma (HCC)
2. Cholangiocarcinoma
3. Angiosarcoma
4. Hepatoblastoma

_____ occurs within the first 2 years of life, and is seen more often in males than in females. It is associated with several syndromes including Trisomy 21, Trisomy 18 and FAP. Increased AFP on labs.

Answer 292

Hepatoblastoma

–may grow rapidly = can rupture and bleed
–Inc. AFP
–sexual precocity may present
(synthesis of ectopic gonadotropin; secondary sex characteristics early)

Question 293

Neoplasms: The most common liver tumor is due to metastasis from another site. However, there are a variety of benign and malignant tumors of the liver. Malignant tumors include:

1. Hepatocellular carcinoma (HCC)
2. Cholangiocarcinoma
3. Angiosarcoma
4. Hepatoblastoma

_____ is the MC primary malignant tumor of the liver. It is increasing in incidence in the U.S. due to cirrhosis-related chronic hepatitis C. It is seen more often in males (4:1) and commonly develops secondary to chronic liver disease.

Answer 293

Hepatocellular carcinoma

*most patients with HCC have pre-existing cirrhosis

Question 294

Neoplasms: In the U.S., patients with HCC are usually older adults in contrast to Asia in which patients infected with hepatitis B at birth develop HCC during young to mid-adulthood.

What are risk factors for developing HCC?

a. Chronic hepatitis B or C infection
b. Chronic alcohol abuse
c. Fatty liver disease
d. Exposure to aflatoxin

Answer 294

All of the above

1. Cirrhosis
   - -chronic hep B, C ***
   - -chronic OH
   - -fatty liver (NASH; NAFD)
   - -hereditary hemochromotosis

Question 295

Neoplasms: True/False - HCC can be acquired due to exposure to aflatoxin, a product of the fungus Aspergillus flavus. It is most often seen in developing countries where grains are stored in hot, humid places.

Answer 295

True

*causes transversion of G to T

Question 296

Neoplasms: HCC is frequently diagnosed late due to the absence of pathognomonic symptoms. As a result, many patients have untreatable disease when first diagnosed, and survival is measured in months.

What are factors that influence (poor) prognosis?

Answer 296

1. Inc. tumor size
2. Vascular invasion
3. Nodal metastasis

Question 297

NeoplasmS: You receive results from a liver biopsy taken from a patient:

Gross
–single mass, multiple nodules OR diffuse infiltration

Histologic:

• -range from well to poorly diff.
• -atypical hepatocytes
• -may be producing bile

The previous describes what disease?

Answer 297

Hepatocellular carcinoma

Question 298

Neoplasms: Paraneoplastic syndromes associated with hepatocellular carcinoma include

1. hypoglycemia
2. erythrocytosis
3. hypercalcemia

_____ is usually seen in advanced disease due to high metabolic needs of the tumor. Secretion of Insulin-like growth factor may contribute.

Answer 298

Hypoglycemia

–typically mild and asymptomatic

Question 299

Neoplasms: Paraneoplastic syndromes associated with hepatocellular carcinoma include

1. hypoglycemia
2. erythrocytosis
3. hypercalcemia

Patients may develop _____ via tumor secretion of EPO

Answer 299

erythrocytosis

*most are anemic due to other effects of tumor

Question 300

Neoplasms: Paraneoplastic syndromes associated with hepatocellular carcinoma include

1. hypoglycemia
2. erythrocytosis
3. hypercalcemia

Hypercalcemia is due to secretion of

Answer 300

parathyroid hormone-related (PTHrP) peptide

Question 301

Neoplasms: HCC most commonly metastasizes hemogenously to what site?

Answer 301

Lungs

other sites:

• -intra-abdominal LN’s
• -bone
• -adrenal gland

Question 302

Neoplasms: A tumor marker for HCC. It is normally produced during gestation by the fetal liver and yolk sac.

It is often elevated in patients with HCC, however, it is neither specific or sensitive for HCC.

Answer 302

AFP (alpha-fetoprotein)

1. Not specific; can be elevated in:
   - -pregnancy, tumors of gonadal origin (yolk sac), other malignancies, viral hepatitis
2. Not sensitive:
   - -not all tumors secrete AFP (esp. smaller tumors)
   - -AFP are normal in fibrolamellar carcinoma

Question 303

Neoplasms: True/False - Diagnosis of HCC can be performed using CT scan with contrast.

Answer 303

True

Question 304

Neoplasms: A distinctive tumor that differs clinically, histologically, and molecularly from conventional HCC. It tends to affect younger patients, and is not associated with cirrhosis or chronic viral hepatitis.

Patients tend to present with abdominal pain or abdominal mass. Serum AFP tends to be normal.

Answer 304

Fibrolamellar carcinoma

• -better prognosis
• -slow growing, resectable
• -histo: tumor cells separated by fibrous tissue

Question 305

Neoplasms: A malignant tumor (adenocarcinoma) of the epithelial cells of the biliary tract.

It is the second most common primary liver malignancy and is most often extra-hepatic (but can be intrahepatic).

Answer 305

Cholangiocarcinoma

*tumors that arise at the hilum (where L. and R. hepatic duct join to form common hepatic) are known as Klatskin’s tumor

Question 306

Neoplasms: Most cholangiocarcinomas are idiopathic, but some are associated with underlying chronic inflammatory processes of the biliary tract, such as:

a. primary sclerosing cholangitis
b. biliary infestation by Chinese liver fluke
c. Choledochal cyst; Caroli disease
d. Choledocholithiasis

Answer 306

all of the above

1. Primary sclerosing cholangitis ***
   - -association with long-standing UC
2. Chinese liver fluke
   - -clonorchis senensis
   - -undercooked fish

Question 307

Neoplasms: Clinical findings of cholangiocarcinoma can be extra-hepatic or intra-hepatic. List examples of each

Answer 307

1. Extra-hepatic
   - -biliary obstruction (acute onset of painless jaundice)
2. Intra-hepatic
   - -less likely to be jaundiced
   - -dull RUQ pain and weight loss

Question 308

Neoplasms: The following labs are suggestive of what neoplasm?

1. Inc. bilirubin (total and conjugated)
2. Inc. Alkaline phosphatase
3. Inc. GGT
4. normal Transaminase
   - -initially normal

Answer 308

Cholangiocarcinoma

• typically follows a cholestatic pattern with regard to labs
• –elevated GGT confirms hepatobiliary origin of excess alkaline phos
• transaminase –may inc. w/ prolonged obstruction and hepatocell. injury

Question 309

Neoplasms: Describe Diagnosis and Treatment of cholangiocarcinoma

Answer 309

Dx:

• -Ultrasound
• -MRI/CT
• -ERCP (circumferential narrowing of distal common bile duct)

Tx:

• -Surgery
• -Biliary stenting

Prognosis
–poor

Question 310

Neoplasms: The MC hepatic tumor is caused by metastasis from elsewhere. Common sites include lung, colon, pancreas, breast

True/False - multiple masses are typical of metastasis

Answer 310

True

Question 311

Neoplasms: Initially liver metastasis is often asymptomatic or presenting first with non-specific symptoms of cancer (weight loss, anorexia). Jaundice is usually absent unless the tumor obstructs biliary flow.

What are signs of advanced disease?

Answer 311

–enlarged, hard, tender liver (massive hepatomegaly) with easily palpable nodules

–peritoneal seeding may produce ascites

Question 312

Liver labs: The following are functions of the liver:

1. Metabolic
2. Synthetic
3. Storage
4. Catabolic
5. Excretory

Explain its actions

Answer 312

1. metabolic
   - -glycogenolysis
   - -gluconeogenesis
2. synthetic
   - -albumin, coagulation factors, other proteins
3. storage
   - -glycogen, TG’s, Fe, Cu, vit. A
4. Catabolic
   - -heme, hormones, drug metabolismt
5. Excretory
   - -bile salts (fat absorption in SI)

Question 313

Liver labs: The lab tests used to evaluate the liver function to:

1. detect the presence of liver disease
2. distinguish b/w the various types of liver disease
3. gauge the extent of liver damage
4. follow the response to treatment

What are shortcomings of the liver lab tests?

Answer 313

1. tests rarely suggest a specific diagnosis
   - –only suggest general category of liver disease
2. batter of tests must be used

Question 314

Liver labs: Lab tests used to evaluate the liver include assessment of:

1. Liver function
2. Hepatocyte injury
3. Bile duct
4. Bilirubin

List tests specific to each

Answer 314

1. Liver function
   - -prothrombin time (PT)
   - -albumin
2. Hepatocyte injury
   - -ALT, AST
3. Bile duct
   - -alkaline phosphatase, gamma glutamyl-transpeptidase
4. Bilirubin
   - -total, conjugated, unconjugated

Question 315

Liver labs: RBC’s and the brain are dependent upon glucose as an energy source. In the fed state, glucose is stored in the liver as _______.

In the fasting state, counter-regulatory hormones (e.g. glucagon, epinephrine) stimulate the breakdown of hepatic glycogen stores into glucose.

Answer 315

glycogen

Question 316

Liver labs: Normal bilirubin production from heme is derived primarily from the breakdown of senescent circulating RBC’s.

1. Extrahepatic bilirubin is bound to serum _______ and delivered to the liver.
2. Hepatocellular uptake of unconjugated bilirubin
3. Glucuronidation in the ER generates _____ monogluronides and diglucuronides that are water soluble and readily excreted in bile
4. Gut bacteria ____ the bilirubin and degrade it to colorless urobilinogens. The urobilinogens are excreted in the feces with some reabsorption and excretion into urine.

Answer 316

1. bound to serum albumin
2. hepatocellular uptake
3. conjugated bilirubin (monoglucuronides and diglucuronides)
   - -USP glycyronyl transferase
4. deconjugate (in terminal ileum)
   * conjugated bilirubin is secreted actively into the bile canaliculus = multi-drug resistance protein 2

Question 317

Liver labs: Total bilirubin = unconjugated bilirubin + conjugated bilirubin.

This equation is referred to as

Answer 317

bilirubin fractionation

*most bilirubin is conjugated

Question 318

Liver labs: Following conjugation in the liver, conjugated bilirubin is stored in the _______where it is subsequently released following stimulation by CCK.

Answer 318

Gallbladder

Question 319

Liver labs: Bile enters the SI at the ampulla of Vater. The conjugated bilirubin remains unchanged until it reaches the terminal ileum and colon where bacteria hydrolyze it into urobilinogen.

What happens to the urobilinogen?

Answer 319

-either reabsorbed into the portal system (sent back to liver/enterohepatic circulation) OR oxidized and excreted in feces (stercobilin) or in urine (urobilin)

Question 320

Liver labs: Physiologic decrease in activity of UDP glucuronyl transferase. It occurs in newborns and is exacerbated by breast feeding.

Answer 320

Neonatal jaundice

*breastmilk – bilirubin-deconjugating enzymes

Question 321

Liver labs - Unconjugated bilirubin: Congenital deficiencies of UDP glucuronyl transferase include:

1. Gilbert syndrome
2. Crigler-Najjar type 1
3. Crigler Najjar type 2

_______ is an AR disorder that results in decreased UGT1A1 (conjugating enzyme) activity. It is the MC inherited disorder of bilirubin glucuronidation. Patients tend to be asymptomatic except for recurrent jaundice from stress (dehydration, fasting, illness, menses).

Answer 321

Gilbert syndrome

• dec. levels of UDP glucuronyl transferase
• patients develop unconjugated hyperbilirubinemia
• clinical course = innocuous (not harmful)

Question 322

Liver labs - Unconjugated bilirubin: Congenital defiencies of UDP glucuronyl transferase include:

1. Gilbert syndrome
2. Crigler-Najjar type 1
3. Crigler Najjar type 2

_____ is an autosomal recessive disorder characterized by absent UGT1A1 activity. It is fatal in the neonatal period.

Answer 322

Crigler-Najjar type 1

*absent enzyme

Question 323

Liver labs - Unconjugated hyperbilirubinemia: Congenital deficiencies of UDP glucuronyl transferase include:

1. Gilbert syndrome
2. Crigler-Najjar type 1
3. Crigler Najjar type 2

_____ is an autosomal dominant disorder with variable penetrance. It is characterized by decreased UGT1A1 activity. Clinical symptoms are generally mild with occasional kernicterus.

Answer 323

Crigler-Najjar type 2

*dec. enzyme

Question 324

Liver labs - Conjugated bilirubin: Congenital defects in canalicular excretion include

1. Dubin-Johnson syndrome
2. Rotor syndrome

_____ is an AR disorder characterized by impaired biliary excretion of bilirubin glucuronides due to mutation in the canalicular multi-drug resistance protein 2 (MRP2)

Answer 324

Dubin-Johnson syndrome

• clinical symptoms: innocuous
• liver - pigmented cytoplasmic globules

Question 325

Liver labs - Conjugated hyperbiirubinemia: Congenital defects in canalicular excretion include:

1. Dubin-Johnson syndrome
2. Rotor syndrome

____ is an AR disorder characterized by decreased hepatic uptake and storage and dec. biliary excretion.

Answer 325

Rotor syndrome

Question 326

Liver labs: True/False - disorders proximal to the conjugated step cause an increase in unconjugated bilirubin, while those distal to the conjugation step cause in increase in conjugated bilirubin

Answer 326

true

Question 327

Liver labs: True/False - Hepatocyte injury (hepatitis) can also contribute to hyperbilirubinemia due to impaired excretion into the bile

Answer 327

True

Question 328

Liver labs: True/False - Intravascular and Extravascular hemolysis are also risk factors for developing unconjugated hyperbilirubinemia

Answer 328

true

*inc. production of bilirubin

Question 329

Liver labs: What do elevated levels of conjugated bilirubin indicate?

Answer 329

• liver (hepatitis) or biliary tract disease

* loss of transport into canaliculi (via MRP2; only energy dependent step in bilirubin metabolism)

Question 330

Liver labs: Hyperbilirubinemia indicates an imbalance between bilirubin production and clearance.

What are clinical manifestations?

Answer 330

1. jaundice
2. scleral icterus (yellow discoloration of sclera)

*cholestasis = systemic retention of bile

Question 331

Liver labs: ______ refers to the accumulation of bile pigment in the hepatic parenchyma. It is due to impaired bile flow either via intrahepatic/extrahepatic obstruction of the biliary tree OR via defective hepatocyte bile secretion.

Answer 331

Cholestasis

*clinical: jaundice, pruritus, intestinal malabsorption (ADEK)

Question 332

Liver labs: What labs would be indicative of cholestasis?

a. Elevated serum alkaline phosphatase
b. elevated y-glutamyl transpeptidase (GGT)
c. elevated ferrochelatase
d. dec. p-ANCA

Answer 332

A and B

-inc. conjugated bilirubin
-inc. serum alkaline phosphatase
-inc. GGT
(enzymes on apical/canalicular membranes of hepatocytes and bile duct epithelial cells)

Question 333

Liver labs: A form of extrahepatic cholestasis that causes obstruction of the common bile from the presence of a gallstone.

It is the MCC of bile duct obstruction in adults.

Answer 333

Choledocholithiasis

*gallstone in common bile duct

Question 334

Liver labs: Which of the following is a risk factor for extrahepatic cholestasis?

a. malignancy of biliary tree (obstruction)
b. carcinoma at the head of the pancreas
c. biliary stricture (secondary to previous surgery)
d. biliary atresia or choledochal cysts

Answer 334

All of the above

*atresia and cysts = children

Question 335

Liver labs: True/False - Extrahepatic biliary obstruction is often amenable to surgical correction. However, prompt diagnosis is imperative since patients are at risk of ascending cholangitis and secondary biliary cirrhosis.

Answer 335

True

Question 336

Liver labs: Occasionally, cholestasis is due to intrahepatic processes involving the bile ducts.

Causes include:

1. Certain drugs and toxins
2. Intra-hepatic cholestasis of pregnancy
3. Autoimmune destruction of intra-hepatic bile ducts (primary biliary or primary sclerosing cholangitis)

Intrahepatic cholestasis of pregnancy occurs late in the second to third trimester. The cause is unknown. What is the outcome?

Answer 336

resolves with delivery

Question 337

Liver labs: _____ is presence of bilirubin in the urine. It indicates an increase in conjugated bilirubin.

This is most commonly caused by biliary tract obstruction and hepatocellular disease.

Answer 337

Bilirubinuria

*unconjugated bilirubin tightly bound to albumin – not filtered by glomerulus

Question 338

Liver labs: In the distal gut, conjugated bilirubin is deconjuagted by bacterial enzymes to form urobilinogen.

1. some is reabsorbed into the portal circulation and is re-excreted
2. some is excreted in feces as stercobilin
3. the remainder is excreted in the urine (urobilinogen)

What causes increased urobilinogen?

Answer 338

1. Hepatocellular damage
   - -liver can’t remove reabsorbed urobilinogen from portal circulation
   - -more excretion by kidneys
2. hemolytic processes
   - -excess bilirubin = more urobilinogen

NOTE: absence of urobilinogen = complete obstruction

Question 339

Liver labs:

1. ________ is found in many different tissues (liver, muscle, kidney). It transaminates aspartate to oxaloacetate. It is NOT specific for liver injury.
2. ______ is found within hepatocytes (cytoplasm). It is a more specific indicator of liver injury.

Answer 339

1. AST (aspartate aminotransferase)
   - -cyoplasm and mitochondria
2. ALT (alanine aminotrasnferase)
   - -inc. = hepatocyte injury (hepatitis)
   - -released in bloodstream upon damage of cell membrane

Question 340

Liver labs: Normal levels of aminotransferases are up to ~40IU/L. Modest elevations (300IU/L) are non-specific, while marked elevations (>1000) typically indicate extensive hepatocellular injury (hepatitis, ischemic injury, toxin-induced or drug injury).

What would suggest alcoholic liver disease?

Answer 340

AST: ALT ratio 2/3:1

NOTE: aminotransferases not greatly inc. in obstructive liver disease

Question 341

Liver labs: Hepatocellular necrosis presents with increased transaminases (ALT > AST) (except alcohol).

Common etiologies include:

1. Ischemic/hypoxic injury
2. hepatitis (viral, OH)
3. Drugs (acetaminophen)

What is seen on histology?

Answer 341

-centrilobular necrosis
(necrosis in center of lobules; around central veins)

–hepatocytes near portal areas (periportal) remain viable

Question 342

Liver labs:

1. Centrilobular (zone 3) necrosis is most confluent with _____ and _____ injuries.
2. Midzonal (zone 2) necrosis is rare, but characteristic of ______
3. Periportal (zone 1) necrosis is characterized by confluent loss of hepatocytes around the portal tract. It is associated with______

Answer 342

1. Zone 3
   - -ischemic injury, acetaminophen induced injury
2. Zone 2
   –rare, characteristic of yellow fever
   (mosquito bite – fever, bleeding)
3. Periportal
   - -ingested toxins

Question 343

Liver labs: Steatosis is the accumulation of fat within hepatocytes. There are two kinds:

1. microvesicular steatosis
2. macrovesicular steatosis

_____ occurs when the cytoplasm is filled with bubbles of fat (does not displace the nucleous). Etiologies include Reye’s syndrome and fatty liver of pregnancy

Answer 343

Microvesicular steatosis

Question 344

Liver labs: Steatosis is the accumulation of fat within hepatocytes. There are two kinds:

1. microvesicular steatosis
2. macrovesicular steatosis

In _______ steatosis, the cytoplasm is replaced by a large bubble of fat which displaces the nucleus to the edge of the cell. Etiologies include: alcohol, DM, and obesity (metabolic syndrome)

Answer 344

Macrovesicular steatosis

Question 345

Liver labs: _________refers to steatosis in the absence of alcohol.

It resembles alcohol-induced liver injury histologically, but occurs within patients with little/no history of OH consumption. Presentation can vary from fat accumulation w/out fibrosis to steatosis with inflammation.

Answer 345

Non-alcoholic fatty liver disease

• may progress to cirrhosis
• commonly associated with obesity (insulin resistance and inc. inflammatory cytokines)

Question 346

Liver labs: True/False - Steatosis alone can be reversed by correcting the metabolic disturbance (e.g. weight loss). However, patients who get inflammation/hepatocyte damage in addition to steatosis (NASH) have increased risk of developing cirrhosis and HCC.

Answer 346

True

Question 347

Liver labs: Enzymes that are elevated in cholestasis are:

1. alkaline phosphatase
2. y-glutamyl transpeptidase (GGT)
3. 5’-nucleotidase

____ can be found in bone and in the placenta as well. It is elevated in kids undergoing rapid bone growth, and in late pregnancy. In cholestasis, it is elevated > 4x normal.

Answer 347

Alkaline phosphatase

• > 4x normal inc w/ cholestasis or infiltrative liver disease (metastatic cancer)

Question 348

Liver labs: Enzymes that are elevated in cholestasis are:

1. alkaline phosphatase
2. y-glutamyl transpeptidase (GGT)
3. 5’-nucleotidase

_____ is MC used to determine if an elevated alkaline phosphatase is due to liver or bone. If both ALP and GGT are elevated, it suggests a liver source.

Answer 348

GGT

*also elevated in alcoholic liver injury

Question 349

Liver labs: Liver labs: Enzymes that are elevated in cholestasis are:

1. alkaline phosphatase
2. y-glutamyl transpeptidase (GGT)
3. 5’-nucleotidase

_____is most often used to determine if an elevated ALP is liver or bone

Answer 349

5’ nucleotidase

Question 350

Liver labs: There are patterns of laboratory abnormalities that help determine cause of liver injury:

1. _____ is disproportionate elevation of the serum aminotransferases compared to alkaline phosphatase/GGT
2. ____ is disporoprtionate elevation of alkaline phosphatase/GGT compared to serum aminotransferases

Answer 350

1. Hepatocellular pattern

2. Cholestatic pattern

Question 351

Liver labs: True/False - To test synthetic function of the liver, albumin can be measured. Albumin is synthesized only by hepatocytes. It has a long 1/2 life (18-20 days) and is thus not the best indicator for acute hepatic dysfuntion.

However, albumin levels <3 g/dL suggest chronic and severe liver disease (e.g. cirrhosis).

Answer 351

True

NOTE: hypoalbuminemia seen in:
–protein malnutrition, protein-losing enteropathies, nephrotic syndrome, chronic infection (prolong inc. IL-1 and TNF inhibit albumin synthesis)

Question 352

Liver labs: Prothrombin time can be used to test synthetic function of the liver. In the case of liver injury, PT time will be prolonged. This is due to the fact that the liver synthesizes the clotting factors (except factor 8 - endothelial cells). These factors have short 1/2 lives (hours to days) w/ factor 7 being the shortest (4-6 hours).

Furthermore, any disorder that leads to deficiency of Vitamin ___ will prolong PT.

Answer 352

Vitamin K defiiency (prolong PT)

Correction w/ Vit. K added: obstructive jaundice, fat malabsorption

Not corrected by Vit. K: acute viral hepatitis, acute/chronic liver diseases
**poor prognostic sign

Question 353

Liver labs: Which of the following is a primary disease of the liver?

a. viral hepatitis
b. non-alcoholic fatty liver disease (NAFLD)
c. alcoholic liver disease
d. metastatic tumor

Answer 353

A-C

*hepatocell. carcinoma

Secondary causes:
–heart failure, metastatic tumor, other infections

Question 354

Liver labs:____ refers to when the liver is unable to perform vital physiologic function. This includes:

1. Loss of protein synthesis
2. Loss of ability to metabolize toxins
3. Impaired glucose homeostasis
4. Loss of ability to clear biliribun

Answer 354

Liver failure

1. Loss of proteins
   - -albumin (lose oncotic -edema)
   - -clotting factors (bleeding)
2. Metabolism of toxins
   - -ammonia (hepatic encephalopathy, asterixis)
   - -alter neurotransmission; brain osmolaility
3. Glucose
   - -hypoglycemia
4. Bilirubin clearance
   - -hyperbilirubinemia (jaundice, scleral icterus)

Question 355

Liver labs: Impaired hemostasis in liver failure involves decreased synthesis of clotting factors and thrombocytopenia.

Dec. synthesis of clotting factor occurs due to impairment of hepatic protein synthesis. What contributes to thrombocytopenia?

Answer 355

• -splenomegaly
• -DIC (consumption of circulating platelets)
• common in hepatic failure
• triggers = liver cell necrosis; inadequate hepatic clearance of activated clotting factors

Question 356

Liver labs: The liver has large functional reserve. To qualify as liver “failure”, the liver has to have lost 80-90% of hepatic function.

It can be acute (<26 weeks) or chronic (>26 weeks). What are causes of acute liver failure?

Answer 356

1. Direct toxic damage
   - -acetaminophen **
2. Combo of direct and immune mediated injury
   - -viral hepatitis

Question 357

Liver labs: _______ is defined as severe acute liver injury with encephalopathy and impaired synthetic function. The MC etiology is acetaminophen overdose. Viral hepatitis (A, B, D and E) is also common.

Answer 357

Acute liver failure

• NOT HCV
• other causes: autoimmune hepatitis, Wilson, ischemic, Budd-Chiari syndrome, mushroom poisoning (Amanita phalloides)

Question 358

Liver labs: A patient presents complaining of nausea, vomiting and abdominal pain. You note jaundice on PE. You also suspect he is suffering from encephalopathy.

Medication: Acetaminophen 3x daily
Labs: 
1. Inc. serum aminotransferases
2. Prolonged PT
3. Hypoglycemia
4. Elevated bilirubin
5. Hypoalbuminemia

What do you suspect?

Answer 358

Acute liver failure

Symptoms:

• nausea, vomiting
• jaundice
• encephalopathy
• coagulation issues
• cerebral edema w/ brain herniation (MC cause of death)

NOTE: serum aminotransferase levels decline w/ recovery or w/ complete loss of hepatocytes

Question 359

Liver labs: Acetaminophen overdose contributes to dose-related hepatic necrosis and hepatic failure.

Normally, acetaminophen binds glutathione, forming non-toxic water-soluble, excrete-able compound (kidneys). In overdose, depletion of glutathione leads to inc. production of the hepatotoxic metabolite (N-acetyl benzoquinoneimine; NAPQI) formed by the cyt P450 system.

What is the treatment?

Answer 359

Tx:
–N-acetylcysteine
(provides SH groups to replete glutathione)

NOTE: alcohol potentiates injury (inc. cyt P450; dec. glutathione)

Question 360

Liver labs: Altered mental status and cognitive dysfunction that is reversible (early).

It occurs as a result of severe liver dysfunction leading to excess ammonia (buildup of nitrogenous waste products) which cause neurotoxicity.

Answer 360

Hepatic encaphalopathy

*NH3 formed from metabolism of aa’s
*NH3 reabsorbed in gut – liver – forms urea
RF: inc. protein load = inc. bacterial conversion **

Question 361

Liver labs: Hepatic encephalopathy progresses in stages:

1. Stage 1: Sleep disturbance, irritability and personality changes
2. Stage 2: ______
3. Stage 3: Deep somnolence
4. Stage 4: ____

This may evolve over days to weeks. Other manifestations include asterixis (flapping motion of outstretched, dorsiflexed hand), slurred speech, ataxia, fetor heptaicus

Answer 361

1. Sleep disturbance
2. Lethargy, disorientation
3. Deep somnolence
4. Coma

Question 362

Liver labs: Rapidly progressive encephalopathy with hepatic dysfunction. It is seen in children following viral illness (e.g. varicella or influenza). It is also associated with ingestion of aspirin.

It causes injury to the mitochondria, resulting in reduced ox phos and fatty acid metabolism (microvesicular steatosis). This ultimately results in inc. ammonia.

Answer 362

Reye syndrome

symptoms:
- -vomiting
- -confusion – rapidly evolve to seizure and coma

Labs:

• -inc. ALT/AST
• -inc. PT, Inc. serum NH3, hypoglycemia, metabolic acidosis

NOTE: DO NOT give ASA to kids w/ febrile illness

Question 363

Liver labs: Long term liver injury (> 26 weeks) that is most often caused by chronic viral hepatitis or cirrhosis.

It presents with anorexia, weight loss, and weakness.

Manifestations may be similar to acute liver failure (though many are asymptomatic until advanced stages of disease).

Answer 363

Chronic liver failure

• complications:
• -Edema (dec. albumin)
• -portal HTN
• -HCC

Question 364

Liver labs: Hepatocyte repair is analogous to other locations in the body. Tissue injury results in scarring (fibrosis).

Injury leads to activation (TGF-B) of the hepatic ____cell, which deposits collagen.

Answer 364

Stellate cell

*normally stores vitamin A

NOTE: cirrhosis = stem cell like hepatocytes that regenerate to form “regenerative nodules”

Question 365

Infections: Most infectious disorders of the liver are secondary to viral infections. Primarily:

1. Hep A (HAV)
2. Hep B (HBV)
3. Hep C (HCV)
4. Hep D (HDV)
5. Hep E (HEV)
   Others: CMV, EBV, HSV, yellow fever

Illness ranges in severity (asymptomatic to fulminant hepatic failure) and patients may be at increased risk of progressing to cirrhosis. What are clinical and laboratory findings for viral hepatitis?

Answer 365

Labs:
1. ALT > AST (variable elevation - 400 to 4000)
(levels peak when patient is icteric; progressive decline)

2. Hyperbilirubinemia
   - -both fractions increased
   - -inc. unconj. bilirubin (b/c dec. uptake and conjugation)
   - -inc. conj. bilirubin (b/c leakage into bloodstream)
   * jaundice = total bilirubin >2.5 mg/dL
3. Inc. urine urobilinogen and urine bilirubin
   - -conj. bil (CB) is water soluble – filtered by kidneys – bilirubinuria
   - -dec. enterohepatic recirculation – inc. urine output

Question 366

Infections: What are clinical findings for acute viral hepatitis?

Answer 366

• -anorexia, nausea, vomiting, abdominal pain

- -w or w/out jaundice (based on bilirubin)

Question 367

Infections: Hepatitis A is an RNA virus that is transmitted via fecal-oral route (fecally contaminated food or water). Incubation is an average of 4 weeks. The following are risk factors for contracting Hep A:

1. International travel (places w/ poor sanitation or sewage Tx)
2. Daycares
3. Oral-anal contact
4. Overcrowding, poor personal hygiene

What are ways of travel-sanitation issues?

Answer 367

1. immunization
2. avoid questionable water sources, raw shellfish, uncooked food
3. wash/peel all fruit
4. boil water or add iodine

Question 368

Infections: Replication of Hep A is limited to the liver. The virus is present in liver, bile, stool and blood.

Fecal shedding/infectivity becomes diminished once the patient becomes jaundiced. What are indicators of acute infection?

Answer 368

1. IgM
   - -initial Ab, (+) before onset of symptoms
   - -peaks during acute phase
   - -persists for few months, disappears when IgG appears
   * *indicates acute infection
2. anti-HAV IgG
   –indefinite
   –indicates immunity (protective antibody)
   (recovery or vaccination)

Question 369

Infections: Treatment of Hep A is mainly supportive because the disease is normally self-limiting.

How is it diagnosed? What is the prognosis?

Answer 369

Diagnosis:

• -Clinical presentation
• -Elevated ALT > AST
• -(+) serology showing presence of anti-HAV abs

Prognosis:

• -more symptomatic in older adults
• -small risk of fulminant hepatitis (death rare)
• -NO chronic hepatitis; no carrier state

Question 370

Infections: Hepatitis B virus is a DNA virus that is transmitted via percutaneous/mucosal contact with blood or body fluids (semen, saliva, vaginal fluid).

RIsk factors include:

1. Sex with an infected partner
2. IVDA (needle sharing)
3. Vertical transmission (mother to infant)
4. Contact with blood or open sores of infected person
5. Occupational exposure (needle stick)
6. Blood transfusion (low risk with current screening).

Incubation is normally around 30-180 days (mean 60-90 days). Clinical symptoms vary from person to person. What are acute manifestations?

Answer 370

1. Asymptomatic
2. Symptomatic
   - -acute hepatitis with jaundice
   - -acute liver failure

Question 371

Infections: True/False: Aminotransferase levels tend to be markedly increased in Hep B infections. They often return to normal within 1 to 4 months.

Answer 371

True

ALT > AST

Question 372

Infections: The serological markers in hepatitis B are

1. HBsAg
2. HBsAb
3. HBcAb
4. HBeAg
5. HBV-DNA

_____ indicates intact virus and infectivity

Answer 372

4. HBeAg
5. HBV-DNA

• infective particles
• appear after and disappear before HBsAg

Question 373

Infections: The serological markers in hepatitis B are

1. HBsAg
2. HBsAb
3. HBcAb
4. HBeAg
5. HBV-DNA

_____ persists for life. It is the best marker for previous exposure to HBV, but does NOT distinguish b/t active and “cured” disease.

Answer 373

HBcAb

*HBcAb IgG - best marker for previous exposure

Question 374

Infections: The serological markers in hepatitis B are

1. HBsAg
2. HBsAb
3. HBcAb
4. HBeAg
5. HBV-DNA

______ indicates past exposure to either HBV or the vaccine. Indicates immunity

Answer 374

HBsAb

• persists for life
• long-term immunity

Question 375

Infections: The serological markers in hepatitis B are

1. HBsAg
2. HBsAb
3. HBcAb
4. HBeAg
5. HBV-DNA

_____ if present, means the patient is producing hepatitis B virus

Answer 375

HBsAg

• 1st marker of infection - 2-8 weeks after exposure
• chronic heptatitis: HBsAg > 6 months

Question 376

Infections: Chronic hepatitis B is signified by HBsAg > 6 months. Age of infection can determine the risk of developing chronicity. It is highest in infants, and lowest in adults.

Ultimately, the end result of chronic infection may be asymptomatic or may have

Answer 376

• -low grade active disease w/ continuing hepatocyte injury

- -may progress to cirrhosis

Question 377

Infections: Possible extra-hepatic manifestations of HBV are

1. polyarteritis nodosa
2. glomerular disease

_____ is necrotizing vasculitis involving the renal, coronary and mesenteric vessels. It spares the pulmonary vessles. It is mediated by circulating immune complexes (Type III hypersensitivty reaction)

Answer 377

Polyarteritis nodosa

Question 378

Infections: Possible extra-hepatic manifestations of HBV are

1. polyarteritis nodosa
2. glomerular disease

______ is usually membranous nephropathy. It is associated with Hep B Ag-Ab complexes in the kidney (type III HSR)

Answer 378

glomerular disease

• proteinuria
• foamy macros
• swelling

Question 379

Infections: The disappearance of HBsAg is followed by the appearance of HBsAb. In some patients, the antibody may not be detectable until after a “window period” of weeks to months.

During this window period, diagnosis may be made by detecting IgM anti-Hbc.

True/False - Anti-HBc IgM presents during acute infection and persists during the “window phase”. It is NOT protective

Answer 379

True

Question 380

Infections: Pre-exposure prophylaxis (PrEP) exists in the form of a Hepatitis B vaccine.

What is post-exposure prophylaxis (PEP) for a non-immune patient who is exposed to Hep B?

Answer 380

1. Hep B Ig
   - -rapidly achieves high titer of circulating anti-HBs

AND

2. Hep B vaccine
   - -long lasting immunity and attenuation of illness

Question 381

Infections: ______ is an RNA virus that is transmitted via body fluids. Its incubation averages ~50 days.

Risk factors include:

1. Past or current IVDA
2. Receipt of a blood transfusion before 1992
3. Occupational exposure (needle stick)

There is NO immunization available

Answer 381

Hepatitis C

*acute infection: 1st 6 months of infection
MC asymptomatic - undetected

Question 382

Infections: Once infected with HCV, patients will either spontaneously clear the virus or go on to develop chronic infection (common). Chronic infection is slowly progressive with many developing cirrhosis.

Chronic HCV is the MCC of chronic liver disease and the most frequent indication for liver transplant in the U.S. How is it detected?

Answer 382

Screening:

1. anti-HCV
   - -initial test
   - -does NOT assess acute, chronic or resolved
   - -is NOT protective Ab

Confirmation:

1. HCV RNA (gold standard)
   - -(+) within 1-2 weeks after infection
   - -used to monitor patients on anti-viral therapy

NOTE: MC HCV genotype is 1a and 1b

Question 383

Infections: An RNA virus that is dependent on HBV (uses Hep B surface antigen as its envelope).

Infectivity includes:
1. Co-infection: can occur with HBV resulting in acute, self-limited hepatitis.

2. Superinfection: when a chonic HBV carrier is subsequently infected with this virus. It may cause severe acute hepatitis.

Answer 383

Hepatitis D (HDV)

• nearly all superinfections develop chronic HDV infection
  (inc. risk of cirrhosis and HCC)

Dx: anti-HDV
*not protective Ab

Question 384

Infections: An RNA virus that is shed in stool during acute illness. It is transmitted by fecal-oral route.

It occurs most often in Asia, Africa and Central America, and zoonotic transmission is the main route of infection.

Answer 384

Hepatitis E

• consumption of uncooked meat
• direct contact with infected animals

Incubation: 3-8 weeks

Question 385

Infections: Hepatitis E causes only mild, non-specific symptoms in most individuals. Immunocompetent individuals tend to clear the virus (and don’t develop chronic infection).

True/False - Severe disease is more frequent in pregnant women (~20%) mortality.

Answer 385

True

Dx:

• anti-HEV IgM (active infection)
• anti-HEV IgG (recovery; *protective Ab)

Question 386

Infections: Symptomatic, biochemical or serological evidence of continuing or relapsing hepatic disease for >6 months.

Likelihood of developing this disease is based on the etiologic agent.

Answer 386

Chronic hepatitis

• never in HAV
• often in HCV (or HBV if acquired early in life)

Question 387

Infections: ______ typically arises following stasis of bile and/or disruption of the normal barrier between the duodenum and bile duct (e.g. ERCP).

It is caused most often by gram negative organisms: E. coli, Klebsiella and Enterobacter.

Manifestations include:
-jaundice, fever, and abdominal pain (Charcot’s triad)

Answer 387

Acute (ascending) cholangitis

Labs:

1. elevated WBC (neutrophils)
2. cholestatic pattern w/ inc. serum alk. phos, GGT and bilirubin (mainly conjugated)

Question 388

Infections: A 38 year old male presents with fever, RUQ pain and tender hepatomegaly.

Blood culture indicates gram negative enteric bacilli.

What do you suspect?

Answer 388

Liver abscess

*gram negative enteric bacilli – hematologic or direct spread

Dx: Imaging (Ultrasound, CT, MRI)
Tx: Drainage, Antibiotics

Question 389

Infections: Entamoeba histolytica infection may be due to ingestion of mature cysts in fecal-contaminated food/water.

Excystation occurs in the small intestine followed by subsequent migration to the large intestine by trophozoites. Which of the following is NOT true about trophozoites?

a. often remain within the intestinal lumen (non-invasive)
b. may invade the intestinal mucosa producing “flask-shaped” ulcers with blood diarrhea
c. can have hematogenous spread to the liver, brain and lungs
d. treatment via combination of antibiotics and respiratory therapy

Answer 389

Answer: D is incorrect

• remain in intestinal lumen
• “flask shaped ulcers”
• spread to liver, brain, lungs

Question 390

Infections: With regard to entamoeba histolytica, areas of highest incidence include:

1. developing countries in tropical areas of the world
   (Mexico, India, Central and South America, tropical Asia and Africa)
2. inadequate sanitation and crowding

How does it present clinically? How is it diagnosed?

Answer 390

Clinical:
–fever, RUQ pain

Dx:

• -Stool (amebic cysts or trophozoites; w/ RBC’s)
• -Serologic tests
• -Imaging of the liver

Question 391

Infections: Infection by this organism is rare in the U.S., but most often occurs in herding populations living in close proximity to dogs and herd animals (sheep, goats, cattle).

Clinical manifestations include:

1. Hydatid cyst of liver
2. abdominal pain
3. palpable RUQ mass
4. may be calcified on imaging

Answer 391

Echinococcus granulosus

• cyst may cause biliary obstruction secondary to mass effect
• may rupture causing anaphylaxis

Question 392

Infections: Long standing infection by liver flukes is associated with an increased risk of adenocarcinoma of the bile ducts (cholangiocarcinoma).

What are the MC types of liver flukes?

Answer 392

1. Fasciola hepatica
   - -sheep liver fluke
2. Clonorchis senensis (Chinese)
   - -varying degrees of biliary obstruction

Question 393

Infections: Schistosomiasis MC occurs in Asia, Africa and S. America.

1. The ____ is the vector
2. Humans become infected when the skin comes into contact with contaminated ____
3. The two types of Hepatic Schistosomiasis are ___ and _____
4. The organisms enter the portal system and lodge within the _______

Answer 393

1. Snail
2. contaminated water
3. Schistosoma mansoni and Schistosoma japonicum
4. Lodge within intrahepatic portal venule
   * granulomatous inflammation and fibrosis around venules (“pipestem fibrosis”)
   * vascular narrowing

**portal HTN

Question 394

Infections: _________ is a type of chronic hepatitis associated with circulating autoabs and elevated Ig concentrations. It predominates in middle aged females, but affects all ethnicities.

It presents as two primary types:

1. Type 1: anti-nuclear (ANA) and anti-smooth muscle abs
2. Type 2: anti-liver/kidney microsome antibodies (anti-LKM)

Answer 394

Autoimmune hepatitis

Clinical (varies)

• -asymptomatic (diagnosed after inc. transaminases)
• -acute liver failure
• -cirrhosis and HCC

Tx: immune suppression

Question 395

Cholestasis: The product of heme breakdown (mostly senescent RBC’s). It is water insoluble, and must be bound to albumin for transport to the liver (where it is conjugated).

Answer 395

Bilirubin

Heme — Biliverdin – bilirubin
heme oxygenase – biliverdin reductase

Question 396

Cholestasis: Unconjugated bilirubin is converted to conjugated bilirubin via UDP-glucuronyltransferase.

True/False - Conjugated bilirubin is water soluble and is actively secreted into the bile canalicul by the MRP2 protein (a.k.a. ATP-binding cassette sub family C; ABCC2).

Answer 396

True

*bile released into lumen of small intestine following ingestion of a meal

Question 397

Cholestasis: Conjugated bilirubin in the small intestine is hydrolyzed into urobilinogen by bacteria within the intestinal lumen (terminal ileum).

What happens to the urobilinogen (3 pathways)

Answer 397

1. Reabsorbed into bloodstream – sent back to liver
   (enterohepatic circulation – recycle bile)
2. Excreted in urine
   - -conjugated
3. Excreted in feces
   - -stercobilin (gives feces its color)
   * defect leads to pale colored stool

Question 398

Cholestasis: _____ describes bile accumulation within the liver. Etiologies include:

1. bile duct obstruction (intrahepatic or extrahepatic)
2. defective secretion of bile from hepatocytes

Answer 398

Cholestasis

Question 399

Cholestasis: Total bilirubin is composed of conjugated (direct) + unconjugated (indirect) bilirubin. It is mostly unconjugated.

What should be done in a patient who has hyperbilirubinemia?

Answer 399

1. determine which fraction (or both) is elevated

* narrows down differential diagnosis

Question 400

Cholestasis: Major causes of unconjugated hyperbilirubinemia include

1. Increased production
2. Decreased hepatic uptake
3. Decreased conjugation (inherited/acquired)

_______ due to increased RBC breakdown (e.g. hemolysis, ineffective erythropoiesis).

Answer 400

Increased production

Question 401

Cholestasis: Major causes of unconjugated hyperbilirubinemia include

1. Increased production
2. Decreased hepatic uptake
3. Decreased conjugation (inherited/acquired)

Decreased hepatic uptake occurs from taking certain medications, while decreased conjugation can be due to decreased enzyme activity, physiologic jaundice, or breastfeeding. Explain

Answer 401

1. Inherited decreased activity of conjugating enzyme
   - -Gilbert syndrome and Crigler Najjar
2. Physiologic jaundice
   - -decreased conjugating enzyme activity in newborns
3. Breast feeding
   - -deconjugating enzyme in breast milk

Question 402

Cholestasis: Conjugated hyperbilirubinemia may be caused by

1. Biliary obstruction/intra-hepatic cholestasis
2. hepatocellular injury
3. inherited disorders

_______ is due to impaired flow of bile into the intestine. Labs reveal elevated conjugated bilirubin and alkaline phosphatase

Answer 402

Biliary obstruction

Question 403

Cholestasis: Conjugated hyperbilirubinemia may be caused by

1. Biliary obstruction/intra-hepatic cholestasis
2. hepatocellular injury
3. inherited disorders

_______ is indicated by reduced secretion of conjugated bilirubin into the bile. Labs reveal predominant elevation of serum aminotransferases

Answer 403

Hepatocellular injury

Question 404

Cholestasis: Conjugated hyperbilirubinemia may be caused by

1. Biliary obstruction/intra-hepatic cholestasis
2. hepatocellular injury
3. inherited disorders

_______ include Dubin-Johnson syndrome and Rotor syndrome. Labs reveal isolated hyperbilirubinemia WITHOUT liver tests abnormalities

Answer 404

Inherited disorders

Question 405

Cholestasis: Clinical manifestations of cholestasis include:

1. jaundice (yellow discoloration of skin and sclera; pruritis). Appears at bilirubin level of ~2.5-3 mg/dL
2. fat malabsorption (steatorrhea, malabsorption of ADEK vitamins)

What would labs reveal in cholestasis?

Answer 405

1. Inc. serum bilirubin
2. Bilirubinuria
   - -CB leaks into circulation – filtered by kidneys and excreted in urine
3. Absent urine urobilinogen
   - -if bile doesn’t enter the gut for bacterial conversion, can’t form urobilinogen
4. Inc. serum alkaline phosphatase and GGT
   - -duct obstruction

Question 406

Cholestasis: Jaundice begins to be appreciated at a bilirubin level of ~2.5-3mg/dL.

What are common disorders associated with jaundice?

Answer 406

1. Hepatitis
   (viral, alcoholic, toxic)
2. Cirrhosis

Question 407

Cholestasis: The following are common causes of unconjugated hyperbilirubinemia?

1. bilirubin overproduction
2. Gilbert’s syndrome
3. Neonatal jaundice

_____ can occur from excessive heme breakdown (i.e. hemolysis), ineffective erythropoiesis (death of hematopoietic cells in bone marrow, OR resorption of a large hematoma.

Answer 407

Overproduction of bilirubin

Question 408

Cholestasis - unconj. hyperbilirubinemia: Gilbert’s syndrome is an inherited disorder characterized by decreased synthesis of UDP-glucuronosyltransferase. Lack of this enzyme results in decreased conjugation of bilirubin with glucuronic acid.

It results in recurrent episodes of jaundice, but otherwise asymptomatic.

What are triggers? How is it Dx? Tx?

Answer 408

Triggers:
–stress, dehydration, fasting, illness

Diagnosis:
–exclude other causes of unconj. hyperbilirubinemia

Tx: None

Question 409

Cholestasis - Unconj. hyperbilirubinemia: Neonatal jaundice is common.

Pathogenesis of neonatal jaundice involves 3 mechanisms:

1. decreased conjugating enzyme activity at birth
2. Inc. bilirubin production (inc. RBC turnover)
3. Inc. enterhepatic circulation at birth
   (undeveloped intestinal flora that converts bilirubin to urobilinogen)

Of these three, what is the most important?

Answer 409

Dec. conjugating enzyme at birth

• total bilirubin peaks at 5-10 (around 2-5 days of age)
• resolves to normal (0.1 -1.2) by 2 weeks
• *Risk of kernicterus if >20

Question 410

Cholestasis - Uncon. hyperbilirubinemia: deposition of unconjugated bilirubin in the brain (basal ganglia) leading to neurological deficits. May lead to fatality

Answer 410

Kernicterus

Tx: phototherapy
–converts biliribuin to water soluble isomers = excreted

Question 411

Cholestasis: Crigler Najjar syndrome is a rare inherited disorder characterized by moderate to marked decrease in conjugating enzyme.

There are 2 types:

1. Type 1 is AR
2. Type 2 is AD

_____ is due to absence of hepatic UDP-glycuronyltransferase activity. It is characterized by markedly increased unconjugated bilirubin.

Answer 411

Type I

• jaundice within a few days of birth
• early neurologic damage (kernicterus) - death

Question 412

Cholestasis: Crigler Najjar syndrome is a rare inherited disorder characterized by moderate to marked decrease in conjugating enzyme.

There are 2 types:

1. Type 1 is AR
2. Type 2 is AD

___ is characterized by moderate decrease in UDP glucuronyltransferase activity. It is less severe.

Answer 412

Type 2

• serum UCB is not as high
• survive into adulthood (no neurologic impairement)

Question 413

Cholestasis - Conjugated hyperbilirubinemia: Conjugated hyperbilirubinemia is mostly due to impaired bile flow.

Impaired bile flow in children may be due to the presence of choledochal cysts or biliary atresia.

What are etiologies for adults?

Answer 413

1. gallstones **MC
2. malignancy of bile duct (head of pancreas)
3. bile duct stricture
4. extrinsic compression (tumpor, lymph node)

Question 414

Cholestasis - Conjugated hyperbilirubinemia: A 4 year old girl presents to the clinic with her mother who states she has been complaining of abdominal pain and vomiting. She also complains of nausea and itchy skin (pruritus).

1. on PE you note jaundice, and a palpable mass
2. Labs: disproportionate inc. of alkaline phos, GGT and bilirubin

Answer 414

Choledochal cyst

• cholestatic pattern
• inc. incidence of stenosis/stricture; cholangiocarcinoma

Question 415

Cholestasis: Multifocal segmental dilation of the intra-hepatic bile ducts. It is often associated with polycystic kidney disease.

Treatment involves surgical resection of the involved lobe and/or liver transplantation

Answer 415

Caroli’s disease

*inc. risk of cholelithiasis, cholangitis, hepatic abscess, cholangiocarcinoma

NOTE: Caroli’s syndrome = bile duct dilation + congenital hepatic fibrosis

Question 416

Cholestasis: A neonatal patient presents with jaundice, pale stools and dark urine.

Labs:

1. inc. conjugated bilirubin
2. inc. ALT/AST
3. Inc. GGT

Cholangiogram reveals absence of uptake within the biliary tree. What do you suspect based on these findings?

Answer 416

Biliary atresia

-progressive fibrous obliteration of extra-hepatic biliary tree

*Cholangiogram = definitive Dx
(if dye appears in the bowel, exclude atresia)

*MC indication for liver transplant in children

Question 417

Cholestasis: Mild, chronic, conjugated hyperbilirubinemia due to defective liver excretion. It presents with a grossly black liver, but is benign.

Answer 417

Dubin-Johnson

*MRPs mutation
impaired secretion of conj. bilirubin = accumulates in hepatocytes

Question 418

Cholestasis: due to impaired hepatic uptake (storage) and excretion of conjugated bilirubin. This results in leakage of CB into the plasma.

Innocuous.

Answer 418

Rotor syndrome

Question 419

Cholestasis - Hyperbilirubinemia: Yellow discoloration of tissue due to deposition of bilirubin. It is particularly well seen in the sclera of the eye, and usually becomes visible at a total bilirubin level of ~2.5-3 mg/dL

Answer 419

Jaundice (icterus)

Question 420

Cholestasis - Hyperbilirubinemia: Darkening of the urine (tea or cola colored) can be seen in patients with hyperbilirubinemia (bilirubinuria).

It may be due to:

1. obstruction of bile outflow (CB leaks into circulation)
2. Hepatocell. disease (can’t secrete CB into bile)

When do we see bilirubinuria?

Answer 420

excess Conjugated bilirubin in the bloodstream

UCB bound to albumin and not filtered by the kidney

Question 421

Cholestasis: Intrahepatic cholestasis is characterized by blockage of the intrahepatic bile ducts.

It is most commonly due to:

1. Drugs **
2. Pregnancy-induced cholestasis
3. Hepatitis

Explain

Answer 421

1. Drugs
   - -oral contraceptives
   - -anabolic steroids
2. Pregnancy-induced
   - -last trimester
   - -resolves after delivery
3. Hepatitis
   * brown pigment within cells

Question 422

Cholestasis: Extrahepatic cholestasis is caused by blockage of the extrahepatic bile duct.

It is commonly associated with:

1. Choledocholithiasis (stone in bile duct; MC)
2. Primary sclerosing cholangitis
3. Extrahepatic biliary atresia
4. Carcinoma at head of pancreas

What are histological features of extrahepatic cholestasis?

Answer 422

Bile within canaliculi

*backup of bile from obstructed biliary drainage

Question 423

Cholestasis: Primary sclerosing cholangitis is characterized by obliterative fibrosis of intrahepatic and extrahepatic bile ducts. It occurs in males < 45 years of age.

It is MC associated with ulcerative colitis (p-ANCA), and can lead to cirrhosis or cholangiocarcinoma.

What are clinical findings of primary sclerosing cholangitis?

Answer 423

Clinical:

• -jaundice
• -pruritus
• -hepatosplenomegaly

Lab:

• -CB > 50%
• -bilrubinuria
• -absent urine urobilinogen
• -inc. alk phos + GGT

Question 424

Cholestasis: A 35 year old male presents with jaundice and complaints of itchy skin. Upon palpation, you note hepatosplenomegaly.

Lab findings include:

1. CB > 50%
2. Bilirubinuria
3. absent urine urobilinogen
4. Inc. alk phos and GGT

What do you suspect? How do you confirm your suspcicion?

Answer 424

Primary sclerosing cholangitis

Dx:

• -ERCP with dye study
• -“beading” narrowing and dilation of bile ducts

Question 425

Cholestasis: Increased blood pressure within the portal vein. It is due to impaired circulation (prehepatic, intra-hepatic and post-hepatic).

Differentiatie between pre, intra and post

Answer 425

1. Pre
   - -obstruction of flow in the portal vein
2. Intra
   - -obstruct flow through liver
3. Post
   - -obstruct flow out of liver

Question 426

Cholestasis: Portal vein thrombosis is a common cause of pre-hepatic portal hypertension.

It is often caused by:

1. Inflammation of the portal vein
2. plycythemia vera
3. hepatocellular carcinoma

Explain how each of these contribute to pre-hepatic HTN

Answer 426

1. portal vein inflammation
   –2ndary to adjacent inflammatory process
   (acute appendicitis)
2. polcythemia vera
   - -inc. blood viscosity
3. HCC
   - -tumor invasion of portal vein

Question 427

Cholestasis: Cirrhosis is the MCC of intrahepatic obstruction and MCC of portal HTN overall.

____ leads to obstruction of the intrahepatic sinusoids, which impedes the inflow of portal blood.

Answer 427

Fibrosis

Question 428

Portal HTN: Centrilobular hemorrhagic necrosis is another cause of intrahepatic obstruction and is usually due to heart failure.

LHF decreases CO which results in hypoperfusion and ischemic necrosis of zone _____ hepatocytes. In addition, RHF causes backup of venous blood.

Answer 428

Necrosis of zone 3

*‘nutmeg” liver

Symptoms:

• -painful hepatomeg +/- jaundice
• -inc. serum transaminases

Question 429

Serummarkers: Aminotransferases

1. ___ inc in most liver disease
2. ____ inc. in alcoholic liver diseae
3. ____ inc. in non-alcoholic liver disease (advanced fibrosis or cirrhosis)

Answer 429

1. ALT > AST
2. AST > ALT
3. AST > ALT suggests advanced fibrosis/cirrhosis

Question 430

Portal HTN: ______ is a cause of intrahepatic obstruction to blood flow and contributes to portal HTN.

It is characterized by cystic, blood-filled cavities throughout the liver. It is rare, and pathogenesis is unclear

Answer 430

Peliosis hepatis

Associations:

• -anabolic steroids
• -bacillary angiomatosis (AIDS, Bartonela)

*usually asymptomatic; potential for hemorrhage

Question 431

Portal HTN: True/False - Sickle cell disease can cause intrahepatic obstruction to blood flow because sickled cells block blood flow

Answer 431

True

Question 432

Portal HTN: Hepatic vein thrombosis (Budd-Chiari syndrome) contributes to post-hepatic obstruction.

It presents with:

1. enlarge, painful liver with portal HTN
2. splenomegaly
3. ascites

How is it diagnosed?

Answer 432

1. Labs
   - -inc. serum transaminases
   - -prolonged PT
2. Diagnosis
   - -US (thrombosis)
   - -CT or MRI for confirmation

NOTE: etiologies - polycythemia vera, hypercoagulable state (protein C/S deficiency), HCC invasion

Question 433

biliary tract and pancreas: Pancreatic insufficiency refers to disease of the exocrine pancreas (e.g. pancreatitis) that impair the adequate release of pancreatic enzymes (lipase).

In the absence of these enzymes, triglycerides cannot be digested to monoglycerides and free fa’s, and thus, cannot be absorbed. What happens to these lipids?

Answer 433

excreted in feces

Question 434

Biliary tract and pancreas: The pancreas releases HCO3- into the duodenum. Chyme coming from the stomach must be neutralized otherwise pancreatic enzymes become inactivated.

What are common causes for acidic pH of chyme?

Answer 434

1. gastrinoma
2. chronic pancreatitis
   - -insufficient secretion of HCO3-

Question 435

Biliary tract and pancreas: True/False - Bile salts are necessary to form micelles and solubilize lipids.

Bile salt deficiency can occur secondary to resection of the ileum, which leads to impaired enterohepatic circulation of bile salts, decreased synthesis of new bile salts, and reduction of the total bile salt pool.

Answer 435

True

*excreted in feces

Question 436

Biliary tract and pancreas:

1. Bacterial overgrowth can lead to _______ of bile salts, reducing their effectiveness.
2. Decreased intestinal cells reduces the _______ area needed for absorption (e.g. celiac)
3. Failure to synthesize apoprotein B results in an inabiity to absorb ______ in the blood

Answer 436

1. deconjugation
2. surface
3. lipids
   - -abetalipoproteinemia

Question 437

Biliary tract and pancreas: Gallstones are comprised mainly of cholesterol (radiolucent). Less common stones include:

1. Black pigment stones
2. Brown pigment stones

______ form by extravascular hemolysis (e.g. hereditary spherocytosis, sickle cell anemia). Macrophages destroy RBC’s leading to increased UCB taken up by the liver. The UCB gets conjugated and is secreted into bile. In the gallbladder, the bilirubin combines with calcium to form calcium-bilirubinate stones.

Answer 437

Black pigment stones

• -calcium bilirubinate
• -radioopaque

Question 438

Biliary tract and pancreas: Gallstones are comprised mainly of cholesterol. Less common stones include:

1. Black pigment stones
2. Brown pigment stones

______ are a sign of CBD infection (infection deconjugates CB into UCB.

Answer 438

Brown pigment stones

• *Asians
• radioopaque

Question 439

Biliary tract and pancreas: Risk factors for gallstones include:

1. Obesity (inc. cholesterol in bile and inc. conversion of androgen to estrogens)
2. Female (pregnancy/sex hormones)
3. Forty (40+)
4. Fertility
5. Familial (Native Americans/Hispanics)

Explain how fertility inc. risk of gallstones

Answer 439

sex hormones supersaturate bile w/ cholesterol

• inc. gallstones
• risk increases w/ inc. # of pregnancies

Question 440

Biliary tract and pancreas: Cholelithiasis (gallstones) occurs when the bile becomes supersaturated and precipitates out as microscopic crystals. These crystals are trapped in the gallbladder mucous forming sludge.

Over time, the crystals grow, aggregate and fuse to form stones. These stones can develop slowly over many years, and remain asymptomatic for decades. What are complications?

Answer 440

1. Acute cholcystitis
   - -if obstruction persists
2. Choledolithiasis
   - -stone migrates to common bile duct and lodges at ampulla of vater
3. Pancreatitis
   - -inc. pressure in pancreatic ducts and injury to acinar cells
   - -auutodigestion of pancreas by pancreatic proteases
4. Acute cholangitis
   - -acute infection due to blockage of common bile duct

Question 441

Biliary tract and pancreas: A 44 year old female presents complaining of intense, steady, dull discomfort in the RUQ or epigastrium. She states the pain is worse after eating, and lasts b/t 30-60 minutes and radiates to the back and shoulder blade. The pain subsides with resolution within 4-6 hours.

She states she sweats a lot and has nausea and vomiting.

What do you suspect?

Answer 441

Biliary colic (manifestation of gallstones)

• post-prandial pain (esp. fatty meal) - gallbladder contracts, force stone against cystic duct opening - inc. pressure
• inc. risk recurrent attacks

Question 442

Biliary tract and pancreas: A patient presents complaining of sudden onset of RUQ tenderness and fever. She states that the pain typically lasts longer than 4-6 hours. She is ill-appearing.

Upon PE you note the patient does not move and guarding occurs. She is positive for Murphy’s sign.

What do you suspect?

Answer 442

Acute cholecystitis (inflammation of gallbladder wall)

• fever and inc. WBC count
• Murphy: inspiratory arrest during deep subcostal palpation of RUQ
• guarding: peritonitis

Question 443

Biliary tract and pancreas: Acute cholcystitis is acute inflammation of the gallbladder wall that usually follows obstruction of the cystic duct by a gallstone.

It elicits the inflammatory response by :

1. Mechanical (inc. intraluminal pressure
2. Chemical (phospholipase acts on lecithin in bile to form lysolescithin)
3. Bacterial (E. coli)

What are complications of acute cholecystitis?

Answer 443

1. gangrene
   - -inc. risk perforation = generalized peritonitis
2. Erosion of gallstone through wall into bowel lumen
   - -obstruction (gallstone ileus)

Question 444

Biliary tract and pancreas: How is acute cholecystitis diagnosed?

Answer 444

1. . Ultrasound = gold standard
   * detects stones, sludge, GB wall thickening
   * cannot ID CBD stones
2. Hepatobiliary iminodiacetec acid (HIDA) scan
   - -visualize biliary tree
   - –won’t see gallbladder if stone in cystic duct
   - -lack of tracer in duodenum indicates CBD stone
   - -dec. ejection fraction of CCK = chronic cholecystitis

Question 445

Biliary tract and pancreas: The MC symptomatic disorder of the gallbladder. It is caused by cholelithiasis (gallstones) with repeated attacks of minor inflammation and mechanical irritation.

Infection is uncommon. Patients may be asymptomatic for years or may progress to symptomatic disease.

Answer 445

Chronic cholecystiti

Symptoms:

• -severe, persistent post-prandial RUQ pain
• -radiates to right scapula

Question 446

Biliary tract and pancreas: Complications of cholecystitis include:

1. _____: progression of acute cholecystitis with continued obstruction and subsequent infection of stagnant bile.
2. _____: prolonged obstruction of the cystic duct leads to distension (mucous) or by clear transudate
3. _____: gallbladder ischemia

Answer 446

1. Empyema
   - -high fever, severe RUQ pain, marked leukocytosis
   - -high risk gram (-) sepsis; perforation
2. Mucocele/Hydrops
3. Gangrene and perforation

Question 447

Biliary tract and pancreas: Complications of cholecystitis include:

4. Fistula formation with bowel segment (duodenum).
5. ______: passage of stone into bowel may lead to bowel obstruction
6. _____: calcium deposits within the wall of a chronically inflamed gallbladder. High association with adenocarcinoma of the gallbladder.

Answer 447

4. Fistula w/ duodenum
5. Gallstone ileus
6. Porcelain gallbladder

Question 448

Biliary tract and pancreas: ____ arises in the setting of chronic inflammation associated with gallstones. It is often discovered incidentally when the gallbladder is removed.

Increased risk is seen in females, Hispanics and Native Americans. It is asymptomatic until late stage and often has a poor prognosis

Answer 448

Adenocarcinoma of the gallbladder

Question 449

Biliary tract and pancreas: _____ are benign yellow deposits of triglycerides and cholesterol in the gallbladder mucosa.

These yellow deposits often appear on a background of hyperemic mucosa “strawberry gallbladder”

Answer 449

Cholesterolisis

Question 450

Biliary tract and pancreas: _____ is the MC congenital anomaly of the pancreas characterized by failure of fusion of the main pancreatic duct (wirsung) with the common bile duct.

Drainage occurs through a small opening.

Answer 450

Pancreas divisum

*predispose to chronic pancreatitis

Question 451

Biliary tract and pancreas: A bind-like ring of normal pancreatic tissue that completely encircles the 2nd portion of the duodenum. It can lead to duodenal obstruction.

It is a rare congenital anomaly.

Answer 451

Annular pancreas

*due to failure of ventral bud to rotate with the duodenum

Question 452

Biliary tract and pancreas: Abnormal embryonic development leading to the presence of pancreatic tissue outside the boundaries of the pancreas, but no anatomic or vascular connection to the pancreas.

It is usually asymptomatic, but the tissue is at risk of the same complications as regular pancreatic tissue.

Answer 452

Ectopic pancreatic tissue

*wall of stomach, SI, Meckel diverticulum

Question 453

Biliary tract and pancreas: _____ is due to injury to the acinar cells of the pancreas or by obstruction of the pancreatic duct. It leads to inappropriate activation of proenzymes within the pancreas, and autodigestion of the pancreas.

Major etiologies:

1. gallstones **
2. alcohol

Answer 453

Acute pancreatitis

• gallstone – obstruct pancreatic duct – inc. pressure – damage to acinar cells – leakage of enzymes – autodigestion
• alcohol – ethanol and metabolites and oxidative stress

Question 454

Biliary tract and pancreas: Alcohol-induced acute pancreatitis may be due to

a. direct destabilization of lysosomes and zymogen granules
b. oxidative stress 2ndary to aggregation of cholesterol esters and fatty acid ethyl esters
c. increased enzyme synthesis
d. dysfunction of the H+/K+ pump

Answer 454

A-C

• cytokines – activate pancreatic stellate cells
• OH directly activates stellate cells

Question 455

Pancreas: A patient presents complaining of abdominal pain with nausea and vomiting. She describes the pain as a dull epigastric ache that radiates to her back. On auscultation you note decreased to nearly absent bowel sounds. Basilar rales present.

Observation of her abdomen reveals discoloration of her flanks and faint discoloration around her umbilicus.

What do you suspect?

Answer 455

Acute pancreatitis

1. Pain: usually sudden, epigastric/periumbiical
2. Bowel: dec. bowel sounds: gastric/intestinal hypomotility
3. Shock: hypovolemia (sequestered fluid)
4. Lungs: pleural effusion (Left side) - circulating trypsin damages pulmonary vasculature, inc. endothelial permeability; destroy pulmonary surfactant (phospholipase A2)
5. Signs: Gray-Turner (flanks; Hb breakdown); Cullen sign (umbilicus; hemorrhage)

Question 456

Pancreas: Patients with pancreatitis may develop hypocalcemia and DIC.

What leads to these?

Answer 456

1. Hypocalcemia
   - -enzymatic fat necrosis
   - -Ca2+ binds fa’s (dec. Ca2+)
   - -inc. tetany
2. DIC
   - -circulating pancreatic enzymes – activate clotting

Question 457

Pancreas: An area of digested pancreatic tissue and fluid around the pancreas. It takes weeks to develop and increases risk of infection.

It is most often due to acute pancreatitis.

Answer 457

Pancreatic pseudocyts

–lined by granulation tissue

**risk of pancreatic abscess (gram neg. - E.coli or pseudomonas)

Question 458

Pancreas: Serum amylase and serum lipase are elevated in acute pancreatitis.

1. _____ is not specific (b/c present in salivary glands). It peaks by ~30 hours and returns to normal in 2-3 days.
2. ____ is specific for pancreatitis. It peaks by 30 hours and returns to normal over 7-14 days.

Answer 458

1. Serum amylase
   - -persistent inc. = necrosis or pancreatic pseudocyst
   - -can be present in urine = may be elevated even when in normal range
2. Serum lipase
   - -not excreted in urine

Question 459

Pancreas: A patient presents complaining of abdominal pain with nausea and vomiting.

Labs reveal

1. neutrophilic leukocytosis
2. Inc. BUN
3. Inc. hematocrit (hemoconcentration)
4. Hyperglycermia
5. Hypocalcemia
6. Abnormal coagulation tests (DIC)

What do you suspect

Answer 459

Acute pancreatitis

1. Hyperglycemia
   - -dec. insulin release
   - -inc. glucagon/catchols

Question 460

Pancreas:

1. ________ is an acute inflammatory response to pancreatic injury. It usually doesn’t cause pancreatic insufficiency. It is associated with inc. serum amylase and lipase.
2. _______ is due to recurrent episodes of acute pancreatitis. It may exhibit symptoms of pancreatic insufficiency (MC exocrine 1st). Serum amylase/lipase may be normal.

Answer 460

1. Acute pancreatitis
   - -diffusely involves large portion of entire pancreas
   - -neutrophils
2. Chronic pancreatitis
   - -patchy w/ mononuclear infiltrate and fibrosis
   - -serum amylase/lipase = not reliable; may be normal

Question 461

Pancreas: A patient presents complaining of epigastric pain that radiates to the back. He states it started as discrete attacks of pain, mostly after eating, but now it is more continuous.

Lab findings reveal:

1. Pancreatic calcifications on plain film/CT
2. ERCP (pancreatic ducal system)
3. Normal - mildly inc. serum amylase/lipase
4. Histology: fibrosis and loss of pancreatic parenchyma

What do you suspect?

Answer 461

Chronic pancreatitis

*deficiency does not occur until > 90% of function lost

Clinical:
1. steatorrhea and type 1 DM (loss of exocrine fxn and endocrine function; dec. ADEK)

2. pancreatic pseudocyst: pancreatic juices enclosed by fibrous/granulation tissue (single/multiple; within or outside pancreas)

Question 462

Pancreas: Chronic pancreatitis causes irreversible destruction of the parenchyma.

In adults, it is MC due to alcohol abuse (though small amount of alcoholics develop chronic pancreatitis; genetic predisposition likely).

In children it is most often associated with Cystic Fibrosis.

What are possible pathologic mechanisms that cause chronic pancreatitis?

Answer 462

1. Inc. pancreatic proteins
   - -protein plugs in ducts
   - -scarring/obsturction
2. Autoimmune injury
   - -autoabs against pancreatic antigen
3. Hereditary

Question 463

Pancreas: A 55 year old African American male presents with complaint of mid-epigastric pain that radiates to the mid/lower back. He states he frequently suffers from nausea, fatigue and loss of appetite. He states he has lost 10 pounds in the past 3 months unintentionally.

PMH: Chronic pancreatitis
PSH: Smoker for 35 years

On PE you note yellow discoloration of the eyes and skin. Trousseau sign (migratory throbophlebitis) present. Gallbladder is palpable.

What do you suspect?

Answer 463

Pancreatic adenocarcinoma

• non-specific symptoms + midepigastric pain
• painless obstructive jaundice (if cancer at head of pancreas)
• venous thrombosis: pro-coagulants from tumor
• palpable gallbladder (Courvoiser’s sign)

Advanced:
–ascites, hepatomegaly (liver mets), Virchow’s node (L. supraclavicular LN)

Question 464

Pancreas: Pancreatic adenocarcinoma usually occurs in older black males and is the 4th leading cause of cancer death. It may be acquired secondary to underlying condition (smoking, chronic pancreatitis), or genetic.

Genetic risk factors include:

1. BRCA
2. Puetz Jeghers
3. Lynch syndrome
4. KRAS mutation (most frequent mutation; inc. MAPK/PI3K/AKT = inc. growth)

Where is the MC location? How is it Dx?

Answer 464

1. Location
   - -MC head of pancreas –block common bile duct (jaundice)
2. Diagnosis
   - -Imaging (abdominal ultrasound and CT)
   - -Biopsy (confirmation)

Question 465

Pancreas: Pancreatic adenocarcinoma is analogous to adenocarcinoma of the colon. It is thought to arise from a precursor dysplastic lesion.

It becomes invasive adenocarcinoma once the lesion invades the stroma.

What labs would we expect to see?

Answer 465

1. Histo
   - –irregular glands within densely fibrotic stroma
2. CA 19-9 increased
   - -biomarker of response to therapy
   - -not specific for screening

NOTE: prognosis is poor b/c symptoms tend to present after metastasis. ~5 year survival (even w/ resection)