Pathoma-Lecture-Notes

Fig - PAS stain in whipple disease (mucin in goblet cells and bacteria inside macrophages
are staining pink)

Abetalipoproteinemia

Defn - Genetic lack of apolipoprotein B-48 and B-100 (autosomal recessive)

Presenta - Absent plasma VLDL and LDL (require B-100)
- Fat malabsorption due to defective chylomicron formation (requires B-100)

Carcinoid tumor - Malignant proliferation of neuroendocrine cells; low grade malignancy

Defn - Can arise anywhere in gut; small bowel most common site
- Grows as submucosal polyp-like nodule
Clinical - Often secretes serotonin (carcinoid syndrome) - asymptomatic as MAO in liver
features metabolizes it to 5-HIAA (see 5-HIAA in urine)

Carcinoid - Seen after tumor metastasizes to liver (bypass hepatic circulation) and
syndrome (HY) secretes serotonin there

Trigger - EtOH or emotional stress that triggers serotonin release

Presentati - Bronchospasm
on - Facial flushing

- Diarrhea
- Carcinoid heart disease - right sided endocardial fibrosis, especially in
tricuspid valve and pulmonary valve (not seen in left heart due to
presence of MAO in lungs)

GI Page 5.4

presence of MAO in lungs)

APPENDIX
Acute appendicitis (MOST COMMON CAUSE OF ACUTE ABDOMEN)

Defn - Acute inflammation of appendix

Cause - Obstruction of appendix by lymphoid hyperplasia (common in kids) and fecolith (common
in adults)

Presen - Periumbilical pain, fever, nausea - pain eventually localizes to right lower quadrant
(McBurney point)
- Rupture results in peritonitis that presents with guarding and rebound tenderness

Complicatio - Periappendicular abscess common complication
n

GI Page 5.5

10.7 Inflammatory Bowel Disease (IBD)

Ulcerative colitis Chorn disease

Wall - Mucosal and submucosal layers - Full thickness with knife like fissures
involve
ment

Locatio - Begins at rectum and - Anywhere from mouth to anus with skip lesions;
n continuously moves back - Terminal ileum most common - Vit B12 deficiency
- Rectum is least common
anywhere up to cecum

Fig: Chorn's (left); UC (right)

Sympto - LLQ pain (rectum) with bloody - RLQ pain (ileum) with non-bloody diarrhea
ms diarrhea

Inflam - Crypt abscess with neutrophils - Lymphoid aggregated with noncaseating granuloma in 50% of

mation cases

Gross - Psudopolyps - Cobblestone mucosa

appear - Los of haustra lead to lead pipe - Creeping fat

ance sign on imaging - Strictures

GI Page 6.1

Complic - Toxic megacolon - Malabsorption (terminal ileum mostly affected)

ation - Carcinoma (depends on extend - Calcium oxalate nephrolithiasis

and duration of disease - no - Fistula formation

problem until >10 years) - Carcinoma if colonic disease present

Smokin - Protects against UC - Increases chance of chron
g

Associa - 10 sclerosing cholangitis (P- - Ankylosing spondylitis, sacroilitis
tion ANCA +ve) - Migratory polyarthritis
- Erythema nodosum

GI Page 6.2

10.8 Colon

Hirschprung disease

Definition Failure of Myenteric (auerbach) plexus and submucosal (Meissner) plexus migration
to distal sigmoid colon and rectum

Association Down's syndrome

Presentati - Presentation based on defective peristalsis/obstruction
on • Failure to pass meconium
• Empty rectal vault on digital rectal exam (DRE)
• Megacolon with risk for rupture

Fig: normally, rectum is bigger than colon
Diagnosis Suction biopsy reveals lack of ganglion cells
Treatment Take the involved bowel out - surgery

Colonic diverticula
Definition Outpouching of colonic mucosa and submucosa through muscularis propria (false
diverticulum)

Cause - Increased wall stress
• Constipation, straining, low fiber diet (increased risk with old age)
• Arise where vasa recta transverses muscularis propria (weak point in colonic
wall)
• Most often found in sigmoid colon

Presentatio - Mostly asymptomatic
n - Rectal bleeding (hematochezia)

- Diverticulitis - due to obstruction of fecal material (appendicitis like symptom on
left lower quadrant)
- Fistula - inflamed diverticulum attaches to local structure

• Colovesicular fistula - presents as air or stool in urine

GI Page 7.1

Angiodysplasia and Hereditary hemorrhagic telangiectasia
1. Differentiate the above two.

Angiodysplasia Hereditary hemorrhagic telangiectasia

Acquired malformation of mucosal and Autosomal dominant disorder resulting thin walled

submucosal capillary beds blood vessels, especially in mouth and GI tract

Mostly seen in cecum and right colon
due to high wall tension

Rupture of capillary beds present as Rupture of blood vessels present as bleeding
hematochezia in old adults

Ischemic colitis (think like MI of colon)

Definition Ischemic damage to colon, mostly at splenic flecture - watershed area of SMA

Cause Artherosclerosis of SMA most common cause

Presentation - Postprandial pain and wt loss
- Infraction results in pain and bloody diarrhea

IBS (Irritable bowel syndrome)

Presentation - Relapsing abdominal pain with bloating, flatulence and change in bowel habits
- IMPROVES WITH DEFECATION
- Increased dietary fiber may help

Prevalence - Classic pt is middle aged women

Cause - Disturbed abdominal motility (no identifiable pathologic change)

GI Page 7.2

10.9 Colorectal Carcinoma

Colonic polyps
1. Differentiate hyperplastic and adenomatous polyps.

Hyperplastic polyp Adenomatous polyp

Most common colon polyp; usually in rectosigmoid Second most common colon polyp
section

Occur due to hyperplasia of glands (polyclonal) - Occur due to neoplastic proliferation of
serrated appearance on microscopy - both are glands (monoclonal)
identical

Benign with no malignant potential Benign but may progress to
adenocarcinoma via adenoma-
carcinoma sequence

2. What is adenoma-carcinoma sequence and what are the steps in it?
- Adenoma-carcinoma sequence describes molecular progression from colonic mucosa to

adenomatous polyp to carcinoma.
- Steps:

Mutation Presentation Gene function

APC (adenomatous increases risk of APC inactivates B-catenin (b-catenin
polyposis coli gene) - polyp formation increases Cyclin D transcription and
sporadic or germline progresses cell cycle)

K-ras leads to formation K-ras works in RAS pathway. One function

of polyp in increase Cyclin D transcription

P53 mutation and increased Progression of P53 transcription factor of p21; prolonged
activation causes transcription of Bax and
COX expression adenoma to lead to apoptosis

carcinoma

- Asprin can be given to stop progression of colon polyp to carcinoma

GI Page 8.1

3. How are screening of polyps done?
- Colonoscopy - both hyperplastic and adenomatous polyp look the same; distinguished by

microscopy
- Fecal occult blood - some polyps bleed

4. What types of polyps have greatest risk of progression to cancer?
- Sessile growth
- Size >2 cm
- Villous histology

Familial adenomatous polyposis (FAP)

Presentation - Presence of 100 or 1000's of adenomatous colonic polyps
- Will progress to cancer by 40 year (remove colon prophylactically)

Mutation - Autosomal dominant
- APC mutation (chromosome 5)

1. Describe the following syndromes associated with FAP.

Gardner - FAP + fibromatosis + osteoma
syndrome - Fibromatosis - usually presents as desmoplasia in retroperitoneum and
destroy local tissue (non-neoplastic proliferation of fibroblasts)
- Osteoma - benign tumor of bone; usually presents in skull

Turcot FAP + CNS tumor (medulloblastoma and glial tumor) - you put turban on head
syndrome

Juvenile polyp, juvenile polyposis and Peutz-Jeghers syndrome
1. Differentiate between the above three.

Juvenile polyp Juvenile polyposis Peutz-Jeghers syndrome
(aka heriditary intestinal

GI Page 8.2

Sporadic, in children <5 years Sporadic or AD (mutation in (aka heriditary intestinal
SMAD - don’t need to know) polyposis)
Usually presents as solitary
rectal hamartomatous polyp Multiple juvenile polyp in Inherited - autosomal
that prolapses and bleeds stomach and colon (juvenile dominant
refers to type of polyp, not age
of pt) - Multiple hamartomatous
polyp in GI tract
- Hyperpigmentation (freckle
like spots) on lips, oral
mucosa and genial skin

Large number increase risk of Increased risk of colorectal,
progression to carcinoma breast and gynecologic
cancer

Colorectal cancer
1. What is colorectal cancer and what's its epidemiology?
- 3rd most common cause of cancer related death
- Peak incidence in 60-70 year olds (both men and women)

2. What are the two molecular pathways that cause CRC?

- Adenoma-carcinoma sequence (most common) Familial adenomatous polyposis (FAP) -
inherited mutation in APC

- Mutation of mismatch repair (MMR)enzymes - Lynch syndrome (inherited mutation in

see microsatellite instability MMR)

3. Describe microsatellite instability's role in CRC. What disorder is associated with microsatellite
instability?

- Microsatellites are repeating sequences of noncoding DNA; their number is maintained during
cell division (i.e. they're stable)

- Instability indicates defect in DNA mismatch repair enzymes
- Disorder associated:

○ Heriditary non-polyposis colorectal carcinoma (HNPCC) - aka Lynch syndrome
 CRC is de novo (not from adenomatous polyps) at early age and usually right sided.

Adenoma-carcinoma sequence HNPCC

80% of sporadic colon cancer

1st mutation - APC - increases chance of polyp Mutation is in DNA mismatch repair
formation enzyme
2nd mutation - K-ras - polyps formed
3rd mutation - COX overexpression and p53
mutation - polyps turn to carcinoma

Cancer progresses from adenomatous polyps Cancer is de-novo (no need to see
adenomatous polyps)

Common age 60-70 Seen early

GI Page 8.3

Common age 60-70 Seen early
Cancer is usually right sided

4. Describe the following features of colorectal cancer.

Location - Right sided - usually see raised lesion; presents as iron deficiency anemia due to
bleeding and vague pain. Older adult with Fe deficiency anemia has colorectal
cancer until proven otherwise
- Left sided -

• napkin ring lesion:
• decreased stool caliber,
• left lower quadrant pain,
• blood streaked stool

Staging - T - depth of invasion (limited to mucosa wont spread away due to lack of
lymphatics)
- N - spread to regional lymph nodes
- M - most common metastasis site is liver

Serum - CEA - used to assess assessing treatment response and detecting recurrence; not
marker useful for screening

GI Page 8.4

Glycogen storage disease

Von Gierke's (Van jerky) Pompe (pump) Cori (coral) Mcardle (muscle glider)
- Type 2 - Type 3 - Type 5
- Type 1 glycogen storage
disease - Lysosomal alpha 1, 4, - Alpha 1, 6, glucosidase - Muscle glycogen
glucosidase aka acid maltase deficiency (glycogen phosphorylase deficiency
- Glucose-6-phosphatase deficiency debranching enzyme)
deficiency (last enzyme in - Presentation:
glycogenolysis) - Presentation: - Presentation: • Severe muscle cramp
• Cardiomegaly • Stunted growth during exercise
- Presentation: • Myoglobinuria
• High glycogen in liver • Increased glycogen in
• Enlarged kidney muscle

• Hepatomegaly - Hepatomegaly • Hepatomegaly - Normal lactic acid
- Severe hypoglycemia - Normal blood glucose - Hypoglycemia
- Lactic acidosis - Hypotonia - Normal lactic acid

1. Von Gierke's disease (Van Jerky)

- Type 1 glycogen storage disease - #1 near Von Jerky

MOA - Glucose-6-phosphatase deficiency - glue with 6P cigar - last enzyme in glycogenolysis reaction

Presentation - High glycogen in liver (glider liver with up arrow)
- Severe hypoglycemia with fasting - liver can't pump out glucose in fasting
- Hepatomegaly (balloon liver)
- Big Kidney (balloon kidney) - glycogen is also stored in kidney
- Lactic acidosis (lake acid with up arrow)

GI Page 9.1

- Lactic acidosis (lake acid with up arrow)
2. Pompe disease (pump)

- Type 2 glycogen storage disease - pump with toto

MOA - Deficiency in lysosomal alpha 1,4 glucosidase (lysol bottle with wand (1), fork (4), glue and daisy bottle) aka acid
maltase (maltese with lemon)

Presentatio - Normal blood glucose - lysosomal breakdown pathway not major source to maintain blood glucose
n - Hepatomegaly

- Cardiomegaly
- Hypotonia - hippo with tonic

3. Cori's disease (coral)

- Type 3 glycogen storage disorder - 3 tree
GI Page 9.2

- Type 3 glycogen storage disorder - 3 tree

MOA - Deficiency in glycogen debranching enzyme alpha 1, 6 glucosidase (saw cutting branch, and afro, wand, saxaphone,
glue with daisy)

Presentatio - Normal blood lactic acid level (body can go gluconeogenesis and some glucose can be taken off glycogn) - lake acid
- n with no up arrow

- Hepatomegaly - glycogen accumulates in liver due to lack of debranching enzyme
- Stunted growth - because body can't mobilize energy source - C clamp
- Hypoglycemia - due to lack of debranching enzyme (hippo-glue bottle)

4. Mcardles disease

- Type 5 glycogen storage disease - hi 5 hand

MOA - Deficiency in muscle glycogen phosphorylase. Enzyme essential for first step in glycogen breakdown. (muscle glider
with phosphate p)

Presentatio - Increased glycogen in muscle (up arrow in glycogen muscle) - glycogen is trapped in muscle
n - Painful muscle cramps with exercise (clamps on muscle man) - due to insufficient glucose to muscle

- Myoglobinuria (mayo globe urinal) - dark, brown urine - without enough glucose, muscle breaks down and releases
myoglobin
- Normal lactic acid (lime with bell curve) - Disease localized only to skeletal muscle and body's overall metabolism
isn't severely affected

GI Page 9.3

Lysosomal storage disorder

1. Hunter and Hurler syndrome Hurlers syndrome

Hunters syndrome - Alpha-L-iduronidase deficiency

- X-linked recessive - Heparan sulfate and dermatan sulfate
accumulates in lysosome
- Iduronate sulfatase deficiency
Presentation:
- Heparan sulfate and dermatan sulfate • Corneal clouding
accumulates in lysosome • Developmental delay
• Gargoylism
Presentation: • Airway obstruction
• No corneal clouding • Hepatosplenomegaly (due to
• Aggressive behavior accumulation of molecules)

a. Hunters syndrome

Genetics - X linked recessive (X on shirt)

MOA - Iduronate sulfatase deficiency - results in abnormal carbohydrate breakdown in
lysosome (Iditarod on sulfur match)
- As a result, Dermatan sulfate accumulates on lysosome (deer tan man)
- Heparan sulfate also accumulates (hippie run)

Presentatio - No corneal clouding (no corn cloud flag)
n - Aggressive behavior (hair pulling)

GI Page 10.1

b. Hurlers syndrome

- Mucopolysaccharidoses disease - a set of disease where body can't break down long
sugar and they accumulate in various tissue and cause disease

MOA - Alpha -L- Iduronidase defeciency - (alpha 1 afro on Iditarod)
- As a result, Dermatan sulfate and heparan sulfate accumulates on lysosome (deer
tan man and hippie run)

Presentati - Gargoylism - flat face, depressed nasal bridge, bulging forehead - gargoyl
on - Airway obstruction - due to craniofacial abnormalities and glycosaminoglycan

deposition in neck tissue
- Corneal clouding
- Developmental delay
- Hepatosplenomegaly

c. Tay Sachs disease (tie with saxophone)

GI Page 10.2

Genetics - Mutation in hexosaminidase A (hexagon tires with mini A) which breaks down GM2
ganglioside (GM2 car)
- Seen more in Ashkenazi jewish population - jew gangster

MOA - GM2 ganglioside accumulates (GM2 car with gangster on side)

Presentatio - Onion skin lysosomes (onion bulb)
n - Cherry red macula (due to accumulation of GM2 ganglioside in retina and

transparency of macula) - cherry on onion
- Progressive degeneration of CNS due to accumulation of GM2 ganglioside (neuron
hands of onion)
- Developmental delay due to GM2 ganglioside accumulation in CNS (developmental
delay bus)

d. Niemann-pick disease (pick in man's knee)

MOA - Deficiency of sphingomyelinase (sphinx on man's leg) leads to accumulation of
sphingomyelin in CNS, liver, spleen.
- More common in Ashkenazi jewish population - jew guy

Presentatio - Foam cells in histology - foam in mouth
n - Hepatosplenomegaly - liver and spleen baloon

- Neurodegeneration
- Cherry red macula - cherry on eyes

e. Metachromatic leukodystrophy

GI Page 10.3

MOA - Deficiency of Arylsulfatase A (arrow sulfur match A). Cerebroside sulfate (cerebro
guy shooting arrow) builds and affect growth of myelin

Presentati - Presentation based on myelin damage
on - Ataxia (taxi)

- Dementia (d man)

f. Gauchers disease (gaucho)

GI Page 10.4

Epidemiolo - Most common lysosomal storage disease
gy

MOA - Deficiency of beta glucocerebrosidase (beta fish, glue, cerebrow guy) leads to
accumulation of glucocerebroside in cell and organs

Presentatio - Gaucher cells - macrophage with glucocerebroside that look like crumpled tissue
n paper - crumpled paper

- Hepatosplenomegaly due to glucocerebroside accumulation.
• Anemia due to RBC destruction in spleen
• Leukopenia and thrombocytopenia

- Bone crisis (crying bone) - severe pain in joints and bone due to glucocerebroside
accumulation
- Erlenmeyer flask deformity - aseptic necrosis of femur that makes it look like
Erlenmeyer flask (necrosis crow with femur)

Fig: Gaucher cell (left), Erlenmeyer flask deformity (middle), normal femur (right)

GI Page 10.5

g. Krabbes disease (Crab)

MOA - Deficiency of galactocerebrosidase (galaxy sign, guy with cerebro) that causes
accumulation of galactocerebroside which damages myelin

Presentati - Globoid cells on histology - enlarged macrophage with multiple nuclei - globe
on - Developmental delay - due to myelin damage- DD bus

- Peripheral neuropathy - damaged nerves
- Optic atrophy - damage to optic nerve fibers - optic atrophy glasses

GI Page 10.6

h. Fabry's disease (febreeze bottle, fairy carrot, fairy wedding)

Inheritance X linked

MOA - Deficiency of alpha galactosidase A (afro galaxy with side A) leads to accumulation

GI Page 10.7

MOA - Deficiency of alpha galactosidase A (afro galaxy with side A) leads to accumulation
of ceramide trihexaside

Presentatio - Globoid cells on histology - enlarged macrophage with multiple nuclei - globe
n - Developmental delay - due to myelin damage- DD bus

- Peripheral neuropathy - damaged nerves
- Optic atrophy - damage to optic nerve fibers - optic atrophy glasses

GI Page 10.8

Chapter 11: Exocrine Pancreas,
Gallbladder, and Liver Pathology

11.1 Exocrine Pancreas

0. What is annular pancreas? (HY)
- Developmental malformation where pancreas forms ring around duodenum.
- Risk of duodenal obstruction

Acute pancreatitis
1. Describe acute pancreatitis, it's etiology, pathophysiology and presentation.
- Acute pancreatitis is reversible enzymatic digestion of pancreas with hemorrhagic damage
(pancreas has lots of blood supply).
- Etiology
○ EtOH and gallstones cause >75% of cases
○ EtOh causes contraction of sphincter of oddi which slows drainage of pancreatic
enzymes --> risking premature activation of enzymes in pancreas
○ Other
 Trauma (ex - automobile accident)
 Hypercalcemia (Ca is activator of enzymes)
 Hyperlipidemia (
 Cystic fibrosis (In CF, low bicarb and water drainage to pancreatic ducts; slow flow
and thick enzyme --> enzyme activation)
 Drugs, scorpion venom
 Mumps
 Rupture of duodenal ulcer
- Pathophysiology
○ Activation of trypsinogen is the first step that cause activation of other enzymes
- Presentation
○ Epigastric pain radiating to back (pancreas is secondary retroperitoneal organ)
○ Nausa, vomiting
○ Periumbilical and flank hemorrhage

Fig - liquifactive necrosis of pancreas with fat necrosis of surrounding fat in pancreatitis

2. How do you diagnose acute pancreatitis?
- Elevated lipase (3 times normal) - most commonly used in diagnosis
- Elevated amylase
- Hypocalcemia - fat necrosis of peripancreatic fat uses up Ca in blood - poor prognotic indicator

3. What is complication of acute pancreatitis?
- Shock - pancreas is very vascular so damage can lead to tons of hemorrhage
- Pancreatic pseudocyst -

Liver and pancreas Page 1.1

- Pancreatic pseudocyst -
○ Pt has abdominal mass with persistent increased in amylase after acute pancreatitis.
Pseudocyst rupture cause release of enzyme and digestion and hemorrhage of gut.

- Pancreatic abscess
○ Usually due to E.Coli. Pt presents with persistently increased amylase.

- DIC - enzymes get on blood, digest coagulation factors
- ARDS - enzymes get to blood, go to lungs and damage alveoli-capillary interface

Chronic pancreatitis
4. What causes chronic pancreatitis?
- Chronic pancreatitis is fibrosis of pancreatic parenchyma which occurs after multiple bouts of
acute pancreatitis
- Etiology
○ EtOH (most common in adults)
○ Cystic fibrosis (most common in kids)
○ Idiopathic
- These etiologies cause repeated attack to pancreas. Other etiology of acute pancreatitis (ex -
hypercalcemia, scorpion bite etc happen only once or so.

5. What are features of chronic pancreatitis?
- Epigastric pain radiating to back
- Pancreatic insufficiency (small fibrosed pancreas)

○ Leads to malabsorption with steatorrhea
○ Fat soluble vitamin deficiency
- Dystrophic calcification of pancreas
- 20 DM in late phase - due to damage of islet cells
- High risk of pancreatic carcinoma

6. Why are serum lipase and amylase not good marker for chronic pancreatitis?
- Because in chronic pancreatitis, pancreas don't produce much enzyme so enzymes aren't

elevated in blood.

Pancreatic adenocarcinoma
7. Describe pancreatic adenocarcinoma, it's risk factor and patient population.
- It's adenocarcinoma arising from pancreatic ducts
- Most commonly seen in elderly
- Major risk factor (HY) -
○ Smoking and chronic pancreatitis

8. What is presentation of pancreatic adenocarcinoma?
- If tumor in head of pancreas - obstructive jaundice with pale stool, palpable gallbladder (blocking

of common bile duct)
- If tumor in body or tail or pancreas - 20 DM
- Acute pancreatitis - due to obstruction of duct
- Migratory thrombophelebitis -

○ Swelling, erythema and tenderness of extremities
- Serum tumor marker is CA 19-9

If you see thin old pt with sudden onset diabetis, suspect pancreatic adenocarcinoma. Because DM is
usually disease of fat people with onset during middle age, and pancreatic adenocarcinoma is disease of
old people.

9. What is prognosis and treatment of pancreatic adenocarcinoma?
- Very poor prognosis (1 year survival <10%)

Liver and pancreas Page 1.2

- Very poor prognosis (1 year survival <10%)
- Treatment is whipple procedure - take out head & neck of pancreas, duodenum and gall bladder

Liver and pancreas Page 1.3

11.2 Gallbladder and Biliary Tract

1. What is biliary atresia? What is its presentation
- Failure to form or early destruction of extrahepatic biliary tree (atresia means

lack of lumen)
- Presentation-

○ Presents with neonatal jaundice (conjugated bilirubinemia) and
progresses to cirrhosis

Cholelithiasis
2. Describe causes of gall bladder stones.

Cholesterol - Very high cholesterol or
stones - low bile acids and phospholipids (bile acid and
phospholipids dissolve cholesterol) (some drugs lower bile
acids)
- Stasis

Pigment stones Pigment stones form due to breakdown of conjugated
- Black bilirubin or too much bilirubin.
stones
- Brown - Black stones - non-bacterial, non-enzymatic
stones breakdown of conjugated bilirubin. One cause -
hemolysis
- Brown stones - bacterial enzymatic breakdown of
bilirubin (stasis can cause bacterial growth in
gallbladder)

3. Describe presentation of cholesterol stones.
- Woman:men = 3:1 Most common stone in western world
- Radiolucent
- 70% of cases are asymptomatic; treat only if symptomatic. 10% of normal popn

have it.

4. What are risk factors for cholesterol stones?
- Age
- Estrogen -

○ Estrogen increases activity of HMG CoA reductase which increases
cholesterol production.

○ Estrogen increases stasis of gall bladder
- Fibrates (Clofibrate) -

○ lipid lowering drug that increases HMG coA reductase.
○ Also decreases conversion of cholesterol to bile acids
- Native American ethnicity
- Chron disease -
○ Most common site for Chron is terminal ileum; that's the site of reuptake

of bile salts and bile acid
- Cirrhosis

5. What's presentation and risk factor for pigment stones (aka bilirubin stones)?
- Presentation

○ Radioopaque
- Risk factors

Liver and pancreas Page 2.1

- Risk factors
○ Extravascular hemolysis (increased bilirubin)
○ Biliary tract infection (bacteria deconjugates conjugated bilirubin)

6. What are some complications of gallstones? (each are described with questions
below)

- Biliary colic
○ Pt has waxing and waning RUQ pain (pain starts when gall bladder
contracts against stone; pain goes away when bladder stops contraction)

- Acute pancreatitis and obstructive jaundice
○ Due to blockage of biliary tree

- Acute and chronic cholecystitis
- Ascending cholangitis
- Gallstone ileus - stone obstructing the intestine lumen
- Gallbladder cancer

Complications of gallstones
7. Describe acute cholecystisis and its presentation?

- Acute cholecystis occurs due to pressure build up in gall bladder due to biliary
tree blockage by stone. Pressure causes squeezing of vessels in gall bladder
wall --> ischemia and bacterial growth

- Presentation
○ RUQ pain that radiates to scapula (HY)
○ Fever with elevated WBC count
○ Increased serum alkaline phosphatase (cell lining biliary tree and gall
bladder contain alk phosphatase)
○ Risk of rupture if untreated

8. Describe chronic cholecystisis.
- Chronic inflammation of gall bladder due to chemical irritation from long

standing cholelithiasis.
- Hallmark - formation of Rokitansky-Aschoff sinus. (HY)

Fig - M resembles gall bladder mucosa. The red circles on bottom
indicates mucosa inside muscular layer (Rokitansky-Aschoff sinus) and it's
not supposed to be there.

9. What is presentation and complication of chronic cholecystisis?
- Presentation

Vague RUQ pain, especially after eating

Liver and pancreas Page 2.2

○ Vague RUQ pain, especially after eating
- Complication

○ Porcelian gallbladder (due to dystrophic calcification of necrotic
gallbladder wall)

Fig - procelian gallbladder.
10. How do you treat chronic cholecystisis?

- Treatment is cholecystectomy
- Treat especially if procelain gallbladder seen (high risk for cancer)
11. Describe clinical features of ascending cholangitis.
- Its ascending bacterial infection of biliary tree often by enteric gram negative

bacteria
- Association

○ Choledocolithiasis (>80% of cases)
- Presentation

○ Charcod's triad (biliary colic (RQU pain), fever, jaundice)
○ Reynaud's pentard (Charcod's triad + hypotension + altered mental

status) - indicates sepsis as opposed to cholangitis only
12. Describe gallstone ileus.

- Due to cholecystitis and fistula formation between gall bladder and small bowel,
stone might enter small bowel and obstruct it.

13. Describe gallbladder carcinoma, it's risk factor, presentation and prognosis.
- It's adenocarcinoma of glandular epithelium of gallbladder wall
- Gallstones are major risk factors, esp with procelain gallbladder
- Presentation
○ Cholecystitis in old woman (cholecystitis is a disease of 40-50 year olds)
- Poor prognosis.

Fig - gallbladder adenocarcinoma

Liver and pancreas Page 2.3

Fig - gallbladder adenocarcinoma
Choledocolithiasis
14. Describe clinical features of choledocolithiasis.

- Stones within the biliary tree
- 90-95% of pt with choledocolithiasis have cholelithiasis. But only 15% of pt with

cholelithiasis have choledocolithiasis.
- Lab finding -

○ Contrast to cholelithiasis, we see sign of biliary tree blockage
 Increased alk phosphatase
 Increased bilirubin

Liver and pancreas Page 2.4

11.3 Liver: Jaundice

1. Explain the pathway of Bilirubin metabolism.

Note: conjugated bilirubin and direct bilirubin are same thing; non -conjugated and indirect are same.

UGT is Uridine glucuronyl transferase

2. What is significance of bile?
- Bile is the only way of cholesterol excretion
- Bile is the main way of copper and iron excretion.

3. What is presentation of jaundice?
- First sign in scleral icterus (yellow sclera). Later see yellow skin
- Occurs due to serum bilirubin >2.5mg/dl

4. Describe the following diseases of hyperbilirubinemia.

Disease Lab values Etiology Clinical features

Extravascular hemolysis High UCB Too much UCB overwhelm liver - Dark urine (increased urobilinogen)
(aka ineffective - High risk for pigmented bilirubin gallstones
hemolysis)
- UCB is fat soluble and can deposit in basal
Physiologic jaundice of High UCB Newborn has transiently low UGT ganglia (kernicterus) leading to neuro defect
newborn and death
- Treatment - phototherapy - makes UCB
Gilbert syndrome High UCB Mildly low UGT activity (autosomal water soluble and can be excreted by kidney
(HY)

- Jaundice during stress (ex - infection);

Liver and pancreas Page 3.1

Gilbert syndrome High UCB Mildly low UGT activity (autosomal - Jaundice during stress (ex - infection);
recessive) otherwise clinically silent
Crigler-Najjar syndrome High UCB
Absent UGT - Kernicterus, usually fatal

Dubin-Johnson High CB Low bilirubin canalicular transport - Dark liver (HY) (otherwise clinically silent)
syndrome protein (autosomal recessive)
Rotor syndrome - Lacks liver discoloration; otherwise same as
Biliary tract obstruction High CB Low bilirubin canalicular transport Dubin-Johnson
(obstructive jaundice) protein (autosomal recessive)
- Dark urine and pale stool
Viral hepatitis High CB Seen with gallstones, pancreatic - Pruritus due to increased plasma bile acids
High alk carcinoma, cholangiocarcinoma, - Hypercholesterolemia with Xanthoma (bile
phosphatas parasites, liver fluke is major way of cholesterol excretion)
e - Steatorrhea with malabsorption of fat
Low urine soluble vitamin
urobilin
- Dark urine (due to CB)
High CB and Inflammation disrupts inflammation - Normal or low urine urobilinogen (CB is
UCB and small bile ductules leaking out to blood and not going to
duodenum)

Notes
- Unconjugated bilirubin can't be excreted by urine as it's fat soluble. It floats in blood until it finds exit.
- Conjugated bilirubin is water soluble, can leak out to blood and will go to urine and make it dark

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11.3 Liver: Hepatitis

1. What are true liver function tests (LFT)?

- True liver function test tests for synthetic ability of liver
○ PT (INR) - most sensitive LFT
○ Albumin
○ Bilirubin

2. What are other LFT?
- Aminotransferases

○ Aspartate aminotransferase (AST) - found in mitochondria. (also increases in muscle injury
and MI)

○ Alanine aminotransferase (ALT) - found in cytosol (better test for hepatocyte injury than AST)

- Alkaline phosphatase - most sensitive test for cholestasis (also present in bone)

3. Some notes on LFT-
- If aminotransferase>alk phos --> hepatocyte injury
- If alk phos > aminotransferase --> cholestatic injury
- If AST>ALT by >2:1 and if both are <300 (IU/L?), suspect EtOH hepatitis
- If ALT>AST, usually viral or NAFLD

4. What does ALT>1000 IU/ml indicate?

- It indicates severe acute hepatitis and has limited etiologies-
○ Shock liver (hepatic ischemia)
○ Drug induced liver injury
○ Acute viral injury

5. What does PT measure?
- Prothrombin time (PT) measures time to convert prothrombin to thrombin. Therefore, it measures

activity of liver derived factors 2, 7, 9 and 10. If pt's PT is low despite enough vit K intake, it's
synthetic dysfunction.

6. What does the following findings indicate?

Findings Indication

Murphy's sign (inspiratory arrest during palpation of RUQ) Cholecystisis

Charcot's triad (RUQ pain, fever, jaundice) Choleangitis

Pruritus Cholestasis

5. What are most common cause of ESLD?
• Hep C
• NASH
• EtOH

6. What are signs of ESLD?
• Increased estrogen (gynecomastia, testicular atrophy) - liver converts estrogen to androgens
• Ascites, jaundice
• Hepatic encephalopathy- asterexis, clonus
• Palmar erythema, spider angiomata

Liver and pancreas Page 4.1

Viral hepatitis
1. What are some causes of viral hepatitis?
- Hepatitis virus A-E (most hep C leads to chronic hepatitis; Hep A,E mainly acute only)
• Acute hepatitis can progress to chronic cases
• Other causes include CMV and EBV

2. Describe presentation of viral hepatitis.
- Presentation-

○ Jaundice (mixed CB and UCB) with dark urine (due to CB)
○ Fever, malaise and nausea
○ Elevated liver enzyme (ALT>AST)
○ Symptoms last < 6 months (if >6 months, it's called chronic hepatitis)

3. Describe histology and pathophysiology of acute viral hepatitis.
- Histology-

○ Viral damage occurs both in between hepatocytes and in portal tracts.
- Pathophysiology-

○ For Hep virus, it's not the virus that causes the damage; it's the CD8 cells that kill
hepatocytes.

4. What is a common complication and histology of chronic hepatitis?
- Complication - Cirrhosis
- Histology - Inflammation predominantly involves portal tract; not much damage to liver

parenchyma.

Fig - L is liver parenchyma, P is portal tract. Note inflammation is mainly in portal tract only.

5. Describe Hep virus A and E.

Hep A Hep E

Transmission - Feco-oral - Feco-oral
- Common in - Commonly acquired from uncooked seafood or contaminated
travelers water

Acute/chronic - Mainly acute - Mainly acute only
only

Active - See Hep E - Presence of IgM marks active infection; presence of IgG marks
infection prior infection that's resolved or immunization (immunization
marker for Hep A only)

Liver and pancreas Page 4.2

marker for Hep A only)

- Hep E in pregnant woman associated with fulminant hepatitis
(liver failure with massive liver necrosis) (HY)

6. How are Hep B and C virus transmitted?
- Parenterally (unprotected sex, childbirth, IV drug, blood transfusion)

7. Describe serologic information about Hep B virus. (HY)
- HBsAG (hep B surface antigen)

○ It is the key and first marker of infection. If it's present disease is present (either active or
chronic).

○ It's the first serologic marker to rise.

- HBeAG and HBV DNA
○ Envelope antigen indicates infectivity of virus.
○ If it's present, pt is highly infectious (can transmit virus)

- HBcAB (hep B core antibody)
○ IgM-
 Indicator of battle between body and hepatitis virus in acute and window stage.
 Major Ab used to defeat the virus
○ IgG-
 If present in absence of HbsAG, it indicates resolved disease
 If present together with HBsAG for >6 months, it indicates chronic hepatitis

- HBsAB (hep B surface antibody)
○ IgG -
 If it's present, then person has won the battle against virus (either it has resolved, or
patient is immunized against it)
 If it's present, then HBsAG will be absent.

8. Which Hep viruses have immunization?
- A, B

9. Describe features of Hep C.
- About 50% of acute cases progress to chronic case with cirrhosis
- Both B and C are leading cause of liver cancer

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10. Describe serology of Hep C.
- Presence of HCV-RNA confirms infection; persistance of HCV-RNA indicates chronic disease

11. Describe Hep D.
- It can't infect by itself and depends on HBV for infection.
- Coinfection - if HBV and HDV infect at same time
- Superinfection - if HBV infects pt with preexisting HDV (more severe than coinfection)

Liver and pancreas Page 4.4

11.3 Liver: Cirrhosis and Tumors

1. Describe cirrhosis.
- It's end stage liver damage characterized by bridging fibrosis (fibrosis between portal tracts) and

regenerative nodules of hepatocytes

Fig - note the regenerative nodules with fibrosis in between - characterstic of cirrhosis.
(normal liver surface is smooth)

2. What mediates fibrosis?
- Stellate cells (that lie below endothelial cells) secrete TGF-beta which mediates the fibrosis.

3. What is presentation of cirrhosis?
- Portal HTN
- Decreased detoxification
- Decreased protein synthesis

4. What are presentation of portal HTN?
○ Ascites
 if SAAG (serum ascites albumin gradient - difference between serum albumin and
ascites albumin) > 1.1 g/dl, 97% accurate for diagnosing ascites due to portal HTN.
 If SAAG <1.1, suspect infection, cancer or inflammation
○ Congestive splenomegaly/hypersplenism
 Spleen eats up RBC because blood is backed up a lot
○ Protosystemic shunts (varices in rectum, esophagus, caput medusa)
○ Hepatorenal syndrome
 Rapidly developing renal failure due to liver failure

5. What are presentation of decreased detoxification?
○ Increased ammonia leads to mental status, asterixis and coma (reversible)
○ Increased estrogen leads to gynecomastia, spider angiomata and palmar erythema (liver
removes estrogen from blood)
○ Jaundice - low metabolism of unconjugated bilirubin

6. What are presentation of decreased protein synthesis?
○ Hypoalbuminemia (leads to edema)
○ Coagulopathy (high PT - due to low function of vit k dependent epoxide reductase)

7. What is the progression of alcohol related liver disease?
- Fatty liver

Fat accumulation in hepatocytes (reversible)

Liver and pancreas Page 5.1

○ Fat accumulation in hepatocytes (reversible)

Fig - white blob of fat in hepatocytes in fatty liver disease.
- Alcoholic hepatitis

○ Direct chemical injury to hepatocytes mediated by acetaldehyde (HY)
○ Generally seen with binge drinking
○ Histology

 Balooning of hepatocytes
 Mallory bodies (characterstic) - damaged intermediate filaments in hepatocytes (HY)
 Inflammation

Fig - circles showing balooning of hepatocyes and mallory bodies characterstic of
alcoholic hepatitis
○ Presentation-
 Painful hepatomegaly with AST>ALT (AST is located in mitochondria and alcohol is
mitochondrial toxin) (HY)
 May result in death
- Cirrhosis
○ Present with signs and symptoms of regular cirrhosis

8. Describe non-alcohol fatty liver disease (NAFLD).
- Can progress from fatty changes to hepatitis to cirrhosis
- Diagnosis of exclusion; ALT>AST
- Associated with obesity

Hemochromatosis and Wilson's disease

Hemochromatosis Wilson's disease
Due to high Fe in body Due to high Cu in body

Liver and pancreas Page 5.2

High risk of cirrhosis and hepatocellular High risk of cirrhosis and hepatocellular carcinoma
carcinoma

Seen in old people Seen in young people

Mutation in gene that regulates enterocyte Mutation in ability to excrete Cu into bile and ability to

Fe metabolism load Cu in ceruloplasmin

9. Describe hemochromatosis.
- Excess iron deposition (hemosiderosis) leads to tissue damage (hemochromatosis)
- Damage due to generation of free radical by Fenten reaction (HY).

10. Describe the MOA of primary hemochromatosis.
- Almost all Fe from diet is absorbed and stored by enterocytes. They regulate how much Iron to
supply to body.
- There's no real way to get rid of Iron (bile and bleeding excretes little bit)
- In hemochromatotis, the regulatory mechanism of enterocytes is lost and all Fe is absorbed.
- Mutation in HFE gene (most commonly c282y) leading to disregulation of enterocytes leads to 10
hemochromatosis.

11. What are some secondary causes of hemochromatosis?
- Receiving blood transfusion

12. What is presentation of hemochromatotis?
- Seen mainly in late adulthood because it takes time for Fe to accumulate.
- Classic presentation is bronze skin, cirrhosis and 20 DM (aka bronze diabetes).
- Other presentations-
○ Increased ferretin, high serum iron
○ Low TIBC (total iron binding capacity) - whenever ferretin is high, TIBC will be low
○ Cardiac arrhythmia, gonadal dysfunction - due to Fe deposition

13. What is liver biopsy finding of hemochromatosis?
- Brown pigments in hepatocytes (looks similar to lipofuscin - normal sign of old cells)
- Prussian blue stain will turn Fe blue, but won't mark lipofuscin

Fig - brown pigments in hepatocytes (maybe hemochromatosis or lipofuscin)

Fig - prussian blue stain showing Fe deposition in hepatocytes
14. How do you treat hemochromatosis? What's its prognosis?

Liver and pancreas Page 5.3

14. How do you treat hemochromatosis? What's its prognosis?
- Blood donation
- Increased risk of hepatocellular carcinoma (due to progression to cirrhosis)

Wilson disease
15. What is wilson disease?

- Autosomal recessive defect (ATP7B gene) that damages hepatocyte Cu transport and decreased
ability to bind Cu to ceruloplasmin (bile main way to excrete Cu; ceruloplasmin Cu carrier in blood)
leads to increased Cu in body.

- Free radical production leads to damage.

16. What's presentation of Wilson's disese? Labs?

- Presents in childhood (contrast to hemochromatosis that presents in adulthood)
○ Cirrhosis
○ Neuro - behavior changes, dementia, chorea, parkinsonism
○ Kayser Fleisher rings in cornea - due to Cu deposition
○ Increased risk of hepatocellular carcinoma

- Treatment - chelating agent

- Labs -
○ High urine copper
○ Decreased serum ceruloplasmin
○ Increased Cu in liver biopsy

Primary biliary cirrhosis and Primary sclerosing cholangitis

Primary biliary cirrhosis Primary sclerosing cholangitis (PSC)

- Autoimmune granulamotous destruction of - Inflammation and fibrosis of intrahepatic and
intrahepatic bile ducts extrahepatic bile ducts

- Associated with other autoimmune disease - Histology shows periductal fibrosis with 'onion
(classic pt women in child bearing age) skinning'
- String and pearl appearance of bile ducts (due to
interspersed fibrosis (string) and inflammation
(pearl)

- Anti-mitochondrial antibody present. (HY) - p-ANCA positive and associated with UC (UC is
also p-ANCA positive) and cholangiocarcinoma.

- Pt present with obstructive jaundice; cirrhosis - Pt present with obstructive jaundice; cirrhosis late
late complication; can cause hepatocellular complication; can cause hepatocellular carcinoma
carcinoma

Fig - preiductal fibrosis with onion skinning seen in PSC

Liver and pancreas Page 5.4

Fig - string and pearl appearance of biliary tree in PSC

Reye syndrome
17. What is reye syndrome?

- Fulminant (severe and sudden onset) liver failure with encephalopathy in children with viral
syndrome that take asprin

- Related to mitochondrial damage of hepatocytes
- Kawasaki disease (vasculitis) affects mainly coronary artery and presents like viral illness in kids.

But asprin is good to use in that case (HY)

18. What's presentation of reye syndrome?
- Hypoglycemia
- Elevated liver enzyme
- Nausea, vomiting
- May progress to coma and death

Hepatic cancer
19. Describe hepatic adenoma.

- Benign tumor of hepatocytes
- Associated with oral contraceptive use; tumor goes down with cessation of drug (HY)
- Risk of rupture because tumor is right below liver capsule - lead to hemorrhage, especially during

pregnancy

20. What are risk factors for hepatocellular carcinoma?
- Chronic hepatitis (usually caused by hep B and C)
- Anything that leads to cirrhosis - hemochromatosis, wilson's, NAFLD, EtOH FLD, alpha-1 antitrypsin
deficiency
- Aflatoxins derived from Aspergillus (HY) - countries that store grains can have Aspergillus grow on
them and they have high incidence of hepatocellular carcinoma
○ Aflatoxin causes mutation in P53 mutation

21. What's relationship between hepatocellular carcinoma and Budd-chiari syndrome?
- Hepatocellular carcinoma loves to invade hepatic vein and cause Budd-chiari
- Presents with painful hepatomegaly and ascites (SAAG <1.1 g/dl)

22. What is prognosis of hepatocellular carcinoma?
- Poor; tumor are detected late as symptoms are masked by cirrhosis

23. What's a serum marker for hepatocellular carcinoma?
- Alpha-fetoprotein

Liver and pancreas Page 5.5

24. Describe cancer metastasis to liver.
- More common than primary liver cancer
- Common source: colon, pancreas, lung, breast
- Presentation:
○ multinodular liver
○ Can feel nodules in free edge of liver in physical exam

Fig - multinodular liver is classic presentation of liver metastasis and can be felt on physical exam

Liver and pancreas Page 5.6

Chapter 12: Kidney and Urinary Tract
Pathology

12.1 Congenital

Horseshoe kidney (no. 1 congenital renal anomaly)
1. What is a finding in horseshoe kidney?
- Kidney abnormally located in lower abdomen as it gets caught in IMA root during its ascent from
pelvis to abdomen.

Fig: horseshoe kidney getting stuck during ascent by IMA

Renal agenesis (failure of kidney to form)
1. Differentiate presentation of unilateral and bilateral renal agenesis.

Unilateral renal agenesis Bilateral renal agenesis (no kidney present) -
incompatible with life

- Hypertrophy of existing kidney; risk of - Oligohydramnios (low amniotic fluid; amniotic fluid
renal failure later in life due to is urine) - presentation called Potter syndrome
hyperfiltration
• Lung hypoplasia (lung develops by stretching
as baby breathes amniotic fluid in and out

• Flat face, low ears, extremity defects (baby
not floating, pressed against mother)

Dysplastic kidney
1. What is presentation of dysplastic kidney? Is it inherited?
- Mostly unilateral and non-inherited malformation of renal parenchyma with cysts and abnormal
tissue (ex-cartilage).
- Congenital but non-inherited
- If bilateral, must be distinguished from polycystic kidney disease

Fig: dysplastic kidney. Circle on left is cyst; circle on right shows growing cartilage
Polycystic kidney disease (PKD)

1. What is presentation of polycystic kidney disease?

Renal Page 1.1

1. What is presentation of polycystic kidney disease?
- Bilateral enlargement of kidney with cysts in renal cortex and medulla
- Inherited

Fig: polycystic kidney disease (note it's always bilateral)

2. Differentiate between autosomal dominant vs autosomal recessive type of polycystic kidney
disease.

Autosomal recessive (aka juvenile Autosomal Dominant (ADult)
form)

- Presents in infants as worsening renal - Presents in young adults with HTN (due to increased

failure and hypertension renin), hematuria and worsening renal failure

- Newborns may have potter sequence

- Associated with (HY): - Associated with:
• congenital hepatic fibrosis (see • berry aneurysm in brain - family history of renal
signs of portal HTN) and disease and brain related death
• hepatic cysts • hepatic cysts, and
• mitral valve prolapse

- Think as cyst in kidney, liver and brain.

- Mutation in APKD1 (adult polycystic kidney disease 1)
or APKD2; cysts develop over time

Medullary cystic kidney disease
1. What is medullary cystic kidney disease?
- Autosomal dominant cyst formation in medullary collecting ducts (PKD has both in cortex and
medulla)
- Parenchymal fibrosis leads to shrunken kidneys (PKD has big disease) and worsening renal failure

Renal Page 1.2

12.2 Acute Renal Failure

a) Classify the types of acute renal failure (azotemia) and its presentation.
- Pre-renal azotemia
- Intra-renal azotemia

○ Acute tubular necrosis (most common cause of ARF)
○ Acute interstitial nephritis
- Post-renal azotemia
- Presentation
○ Azotemia - hallmark (increase BUN in blood; uremia is symptoms due to increased BUN)
○ Oliguria (if we make <500ml urine/day, we can't excrete solid waste)

b) What are come causes of increased serum BUN?
- Decreased kidney function
- Use of steroids
- Upper GI bleed (blood has proteins and their metabolism can lead to nitrogenous waste build up)
- Hypercatabolic state (sepsis, critical illness)
- Dehydration, volume depletion.

Pre-renal azotemia (ARF)
b) Describe pre-renal azotemia and lab findings.
- Azotemia caused due to decreased renal perfusion.
- Causes - hypotension, decreased effective circulating volume, renal ischemia
- Lab findings -
○ FENa <1% (amount of excreted sodium in the urine)
○ Bun/Cr >15 (high)
○ High urine osmolality (>500) and low urine sodium

c) What is normal Bun/Cr ratio and how does it change during azotemia?
- Normally, Cr is excreted a little in PCT, and Bun is reabsorbed in PCT. Therefore, BUN is higher in

blood than Cr which makes normal BUN:Cr = 15
- In pre-renal azotemia, RAAS is activated due to decreased renal perfusion. More water is

reabsorbed, and more BUN is reabsorved with it. Therefore, BUN/Cr>15.
- In intra renal and post renal azotemia, Cr isn't excreted well. Build up of creatinine makes

Bun:Cr<15. (is this reasoning right)

d) What does FENa tell us?
- FENa = (urine Na/serum Na) / (urine Cr/serum Cr). It tells if kidney is dead or holding onto every

bit of salt it can. Lower it is, the better. If <1%, indicated pre-renal ARF.

Post-renal azotemia
e) Describe post-renal azotemia.
- Due to obstruction of urinary tract downstream, GFR decreases and results in azotemia, oliguria.
- Presentation
○ Early stage - FENa<1%, and BUN:Cr>15 (because increased backflow pushes BUN back to
blood.
○ Late stage - FENa>2%, BUN:Cr<15, and urine Osm<500 due to tubular damage and kidney
not working well.

Intra-renal azotemia (ARF)

Renal Page 2.1

Intra-renal azotemia (ARF)
a) Describe causes of intra-renal azotemia.
- Acute tubular necrosis
- Acute interstitial nephritis

b) Describe features of acute tubular necrosis (most common cause of ARF)?
- Necrotic tubular cells clog tubules, decrease GFR
- Hallmark - brown granular casts seen in urine
- Don't see inflammatory cells. If you see it, suspect acute interstitial nephritis

Fig- ATN - T are tubules that are clogged up by dead cells. G is glomerulus.

c) What are lab values for acute tubular necrosis?
- Bun:Cr <15 because BUN can't be reabsorbed
- FENa >2% because kidney not working well
- Urine osmolality <500 because kidney can't concentrate urine
- Azotemia, oliguria
- Hyperkalemia with metabolic acidosis (increased anion gap)

i) What are etiologies of acute tubular necrosis?
- Ischemic etiology - often preceded by prerenal azotemia. PCT and thick ascending limb are

particularly susceptible to ischemia
- Nephrotoxic etiology - PCT particularly susceptible

○ Heavy metal (lead
○ Myoglobinuria (crush injury
○ Antifreeze (ethylene glycol) - pt have oxalate crystal in their urine (HY)
○ Radiocontrast dye (iodine)
○ Aminoglycosides
○ Urate (chemotherapy drug if kills lots of tumor cells at once, damage of nucleic acids make

uric acid which can cause ATN (HY))

j) What is prognosis of ATN?
- Tubular cells are stable (can regenerate if needed). So support by dialysis because electrolyte

imbalance can kill. Otherwise, you can expect full recovery.

k) Describe acute interstitial nephritis. What are some drugs that can cause it?
- An intra-renal cause of ARF.
- Hallmark is presence of inflammatory cells in kidney interstitium.

Renal Page 2.2

- Hallmark is presence of inflammatory cells in kidney interstitium.
- Causes -

○ most common is infection or allergy
○ Others- toxin, disease
○ Drugs - commonly penicillin, diuretics, NSAIDs
- Eosinophils and monocytes are seen in drug induced AIN and polymorphonuclear nucleocytes are
seen in infectious AIN.
l) What is presentation of acute interstitial necrosis?
- Oliguria, fever, and rash days-weeks after infection/drug start
- Resolves with cessation of drug/infection
- May progress to renal papillary necrosis
m) What is renal papillary necrosis?
- Necrosis of renal papillae
- Presents with gross hematuira and flank pain
- Causes -
○ Analgesic abuse
○ DM
○ Sicke cell
○ Severe acute pyelonephritis
4. Describe autosomal dominant posycystic kidney disease.
• Third most common cause of renal failure
• Mutation in PDK1 is most common cause
• Presentation-
○ Hematuria, HTN, circle of Wills berry aneurysm
○ Azotemia
○ Dull loin pain (kidneys are super huge and can be easily palpated)

Renal Page 2.3

12.3 Nephrotic Syndrome

Nephrotic syndrome
1. What are presentation of nephrotic syndrome?
 Hallmark is >3.5g protein/day in urine
 Hypoalbuminurea
 Hypogammaglobulinemia
 Hypercoagulable state - loss of antithrombin 3
 Hyperlipidemia and hypercholesteremia - liver dumps fat to blood to make it thick (compensate
for loss of disease)

2. Describe minimal change disease.
• So common in kids that kids with nephrotic syndrome are assumed to have it.
• Cause - mostly idiopathic or may associate with hodkin's lymphoma (HY) - due to massive

production of cytokines.
• Sudden onset of symptoms, normal creatinine, normal renal function, normal BP. Not much

symptom other than nephrotic syndrome (that's why called minimal change).
• Change is so minimum that mainly albumin is lost, no immunoglobulin loss.
• Diagnosis - diagnosis of exclusion
• Histology -

○ glomerulus normal in light microscope, immunofluorescence.
○ EM shows microvillus transformation and effacement of foot process (a nonspecific finding

seen in all nephrotic diseases)
• Treatment- excellent response to steroids because disease caused by cytokines from active T cells.

Steroids reduce cytokine production
• Prognosis - often recur

Fig - effacement of foot process. Bottom part is capillary; black blobs are RBC.

3. Describe presentation of FSGS.
• Most common cause of nephrotic syndome in hispanics and blacks.
• Risk factors - most common in people with AIDS, heroin and sickle cell disease (HY). However,

most disease are idiopathic.
• Diagnosis - No serology, do biopsy. See focally segmental glomerulus.
• Treatment - not great but treat with steroids, immunosuppresants, control BP

4. Describe biopsy finding in FSGS
• Glomerulus is sclerosed (hardened) by hyalinosis (proteins and lipid deposition) in focal (only

some glomerulus affected - <50%) and segmental (only a part of glomerulus is affected) pattern.

Renal Page 3.1

Fig - Only bottom right glomerulus is affected segmentally.
• Sclerosis seen in H&E and hard to see in PAS or silver stain
5. Describe membranous nephropathy.
• Most common primary nephrotic syndrome. Often seen in old people
• Presentation:

○ Very severe nephrotic syndrome
• Treatment - very difficult to treat. 20-30% progress to end stage renal disease
• Secondary causes

○ Hep B>C (HY)
○ Lupus
○ Lung and colon cancer
○ Heavy metal
• Diagnosis - no serology; need biopsy
5.5. Describe relationship between lupus and membranous nephropathy (HY).
 Most common cause of death in patients with lupus is renal failure due to diffuse proliferative
glomerulonephritis (a nephritic syndrome). However, if lupus pt develop nephrotic syndrome,
they'll get membranous nephropathy.
6. What are histologic findings of membranous nephropathy?
• Capillary wall (basement membrane) thickens due to immune deposition; hence the name
membranous - see on H&E
• Any time there's membranous in name, there's immune deposition and thick glomerulus
membrane.

Fig - capillary wall thickening in MN.
• Small and frequent subepithelial deposition (IgG or C3 depositis)

○ Deposits give spike and hole appearance in PAS or silver stain

Renal Page 3.2

Fig - notice the small spikes and holes on PAS or silver stain. Holes are immune deposits as
they don't bind to silver. Spikes are new basement membrane laid on top of holes. They bind
to silver and stain dark.
○ Small and frequent deposits seen in EM. Immune deposition is subepithelial (below
epithelium - podocytes also called epithelium)

FIg - the dark deposits are immune deposits seen in MN.
○ Immune deposit is granular so immunofluorescence is granular

Fig - granular immunofluorescence seen in MN due to C3 and IgG immune deposite
7. Describe histology of Membranoproliferative glomerulonephritis (cause nephrotic or nephritic or

both).
• Membranous implies thick capillary membrane and immune deposition
• Proliferative means mesangial cell in glomerulus proliferate
• Thick capillary wall makes tram track appearance on H&E. Proliferation of mesangium cuts the

immune deposit in half creating two lines (tram tracks)

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