Path Exam 3- Liver and nutrition Flashcards
Non-alcoholic hepatitis/necrosis LFT
ALT & AST
- both ~10x UL
- greater than alkaline phosphatase
- DIRECT bilirubin ↑ → indirect ↑ (jaundice)
- -urine urobilinogen ↑
Alk phos & GGT- relatively normal
Chronic hepatitis:
-Prolonged PT/PTT (no improvement w/ vit K)
Alcoholic hepatitis/necrosis LFT
ALT & AST
- AST 2x greater than ALT (↑ AST in rhabdomyalysis)
- both ~10x UL
- larger than alkaline phosphatase
- DIRECT bilirubin ↑ → indirect ↑ (jaundice)
- -urine urobilinogen ↑
- *GGT ↑↑ due to microsomal induction
- **neutrophilic leukocytosis
- Mallory bodies: intracytoplasmic eosinophilic bodies
- -irregular size & shape
- -from cytokeratin damage
Cirrhosis/ chronic liver failure LFT
- ALT & AST ↑
- alk phos ↑
- Hypoalbuminemia**
- ↑ PT/PTT (no improvement w/ vit K)
- Ammonia ↑↑ (Tx: lactulose- traps ammonia)
- INDIRECT hyperbilirubinemia (variable)
- anemic
- Cholic acid ↓ (reduced ratio of 1ry : 2ry)
Cholestatic LFT
- Alk Phos & GGT ↑↑
- direct bilirubin ↑ → cholestatic jaundice
- serum cholesterol ↑ → xanthomas
- retained bile salts → pruritis
- *-malabsorption; vit déficiences A, D, K
- -if K deficient → prolonged PT/PTT that reverses w/ K
Fulminant failure LFT
- AST & ALT ↑↑↑
- Ammonia ↑↑ (Tx: lactulose- traps ammonia)
- **Ferritin ↑↑↑
- hypoalbuminemia
- PT/PTT prolonged (no improvement w/ vit K)
- DIRECT hyperbilirubinemia (variable)
- -urobilinogen ↑ in urine
onset of symptoms → hepatic encephalopathy w/in 2-3 weeks
Space occupying lesion LFT
↑ T. Bili & Direct Bili
-no other significant changes
Acute Liver Failure causes
A: acetaminophen, HAV, autoimmune
B: Budd-Chiari, HBV
C: copper (Wilson’s), HCV
D: drugs/toxin, HDV
E: HEV in pregnancy
F: fatty- microvesicular type (no hepatic necrosis)
–tetracycline, valproate, pregnancy, Reye syndrome
Acute HBV serology
1) HBsAg rises (falls in acute) → Anti-HBs rises (immunity)
2) anti-HBc IgM → anti-HBc total (does not confer immunity)
3) HBeAg rises (falls before sAg)→ Anti HBe
HBeAg: infectivity; active viral replication
-persistence = progression, ↑ risk HCC
HBe-Ab → cessation of proliferation, good sign
Hbs-Ab → immunity
Chronic HBV serology
- 1) HBsAg rises and remains elevated (NO Anti HBs)
2) anti-HBc IgM → anti-HBc total (does not confer immunity) - 3) HBeAg rises (falls LATER)→ Anti HBe appear later
HBeAg: infectivity; active viral replication
-persistence = progression, ↑ risk HCC
HBe-Ab → cessation of proliferation, good sign
Hbs-Ab → immunity (doesn’t appear in chronic)
Three characteristics & top 3 causes of Cirrhosis
1) Bridging fibrous septa
2) Parenchymal nodules (micro & macro)
3) Disruption of architecture of entire liver
top 3 causes: -Alcoholic liver disease -Viral hepatitis -Non-alcoholic steatohepatitis (+ HCC = 4 primary liver insults)
HBV extrahepatic manifestations
- membranous GN
- most common assoc. w/ polyarteritis nodosa
- -vasculitis → ischemia → nerves, GI, kidney
- –aneurysms
- serum sickness syndromes
- -arthralgias, proteinuria, cutaneous eruptions, GI disease
HCV extrahepatic manifestations
- Cryoglobulinemia
- -raynauds, arthralgias, purpura
- Membranoproliferative GN
- Sporadic porphyria cutanea tarda (sensitive to sun)
- ↑ type II DM
- cutaneous vasculitis, leukocytoclastic
- serum sickness syndromes
- -arthralgias, proteinuria, cutaneous eruptions, GI disease
Clinical features of liver abscess
- Fever
- RUQ pain & tender hepatomegaly
- Alk phos ↑
- AST/ALT ↑ mild to moderate
- jaundice if biliary system obstructed
AI hepatitis
Labs:
- ANA, SMA,
- children- LKM1
Morphology:
- plasma cells
- 78% female
- interface hepatitis (piecemeal necrosis)
- -necrosis b/w periportal parenchyma & portal tracts
- bridging/necrosis fibrosis- b/w portal tracts
- lymphoid infiltrates of portal tracts (dense mononuclear)
- reactive bile duct changes
alpha-1 anti-trypsin deficiency
Labs:
- PiZZ
- -accumulation of misfiled Pi protein in cyto. of hepatocytes
Morphology:
- *-PAS+
- globular round eosinophilic inclusions
- mallory bodies
- *-Neonatal hepatitis** w/ cholestatic jaundice
- clinically silent until cirrhosis in late life
- ↑ risk HCC w/ or w/o cirrhosis
- Associated w/ emphysema
- prolonged conjugated bilirubinemia (dark urine, light stool)
- most infants recover
NASH
NAFLD → NASH → NASH cirrhosis
↓ ↓ ↓
isolated HCC HCC or Decomp
Wilson’s disease
Labs:
- Ceruloplasmin ↓
- urine Cu ↑
- ATP7 mutation
Morphology:
- Cu accumulation
- **Macronodular cirrhosis
- Kayser-Fleishcer rings (limbus)
- symptoms won’t appear until at least ~10yrs
- Degeneration of lenticular nu. (putamen)
- choreoathetoid movements
- vacuous smile
- drooling
Hemochromatosis
Labs:
- HFE mutated→ hepcidin dysreg.→ excess absorption
- % saturation ↑↑ (ferritin ↑↑)
Morphology:
- micronodular cirrhosis
- stain w/ prussian blue
Symptoms usually appear around 40 yrs Classic Triad: 1) Pigment cirrhosis of liver --HCC → free radicals (200x risk) 2) Skin pigmentation 3) DM → loss of islet cells
- Hypogonadism (pit-hypothalm axis disruption)
- -amenorrhea
- -loss of libido / impotence
- Cardiomyopathy → arryhthmias
- arthritis / pseudogout
HBV morphology (acute & chronic)
ACUTE HEPATITIS (mimicked by drugs & AI hep)
- T-cell infiltrates in lobules
- ballooing degeneration → cholestasis
- apoptosis: acidophil (councilman) bodies
- lobular disarray
- cholestasis
CHRONIC HEPATITIS
- **Ground glass
- interface hepatitis (piecemeal necrosis)
- -necrosis b/w periportal parenchyma & portal tracts
- bridging/necrosis fibrosis- b/w portal tracts
- lymphoid infiltrates of portal tracts (dense mononuclear)
- reactive bile duct changes
HCV morphology (acute & chronic)
ACUTE (mimicked by drugs & AI hep)
- T-cell infiltrates in lobules
- ballooing degeneration → cholestasis
- apoptosis: acidophil (councilman) bodies
- lobular disarray
- cholestasis
CHRONIC HEPATITIS
- **Steatosis
- interface hepatitis (piecemeal necrosis)
- -necrosis b/w periportal parenchyma & portal tracts
- bridging/necrosis fibrosis- b/w portal tracts
- lymphoid infiltrates of portal tracts (dense mononuclear)
- reactive bile duct changes
Blood alcohol levels
80 mg/dl (0.08) → DUI
200 mg/dl (0.2) → inebriate occasional drinker
300-400 mg/dl → coma & respiratory arrest in unhabituated drinker
700 mg/dl → tolderated in habitual drinkers
Thiamine (B1) deficiency
- Wernicke-Korsakoff syndrome
- Dilated cardiomyopathy, high output failure (wet beriberi)
- polyneuropathy (dry beriberi)
- -toedrop, footdrop
- weight loss
- muscle wasting
- edema
Riboflavin (B2) deficiency
- Interstitial keratitis: vascularization of cornea
- Greasy, scaling dermatitis
- Erythroid hypoplasia
- Glossitis
- Cheilitis / Cheilosis
Niacin (B3) deficiency– Pellegra
3 D’s
- dermatitis- SUN EXPOSED; scaling, desquamation, fissures
- diarrhea- intestinal mucosal atrophy
- dementia (neuronal loss)
- -degeneration of posterior & lateral columns
- death
- glossitis
-carcinoid syndrome (uses up Tryptophan for serotonin)
Pyridoxine deficiency
- peripheral neuropathy
- convulsions: can only be stopped by pyridoxine
- cheilosis
- glossitis
- ↑ plasma homocysteine
-long term use of isoniazid or estrogen
Vit. C deficiency
- perifollicular rash
- bleeding gums
- joint pain
- subperiosteal bleed
- impaired wound healing
- anemia
-scorbutic rickets in children
Folate (B9) deficiency
Due to:
- ↑ use: pregnancy
- Interference w/ absorption/metabolism
- -ALCOHOL
- -smoking
- -oral contraceptive
- -anticonvulsants
- -chronic disease
- Spina bifida / neural tube defects in fetus
- megaloblastic anemia
- Hyperhomocysteinemia: ↑ risk coronary thrombosis & stroke
B12 deficiency
Due to:
- loss of intrinsic factor
- -AI gastritis
- -gastric bypass/resection
- malabsorption disease; crohn’s
- parasite
- Degeneration of spinal cord myelin
- -sensory-motor defects (vibratory first lost)
- Hyperhomocysteinemia: ↑ risk coronary thrombosis/stroke
- glossitis
- megaloblastic anemia (low platelets & PMN)
Copper deficiency
Due to:
- gastric surgery
- intestinal malabsorption**
- excess zinc
- Myeloneuropathy
- -muscle weakness & neurologic defects
- abnormal collagen cross-linking
(malabsorption + neuropathy → Copper)
Zinc deficiency
Acrodermatitis enteropathica
- dermatitis around ORIFICES (eyes, nose, mouth
- dermatitis of distal extremities
- hypogonadism
- impaired night vision
- impaired immunity & healing
Selenium deficiency
Protects against oxidative injury of lipids w/ vit E
-component of GSH-peroxidase
- myopathy
- cardiomyopathy in women & children (Keshan disease)
- Narrow therapeutic window: significant toxicity
- -↑ risk of prostate cancer in men
Vit. A deficiency
Vit. A maintains specialized epithelium
- Night blindness (earliest sign): ↓ rhodopsin regen.
- Bitot spots: build up of keratin
Squamous Metaplasia
- -conjuctiva → xeropthalmia
- -cornea → keratomalacia → scarring→ blind
- -bronchus → bronchopneumonia
- -urinary tract → kidney stones
- -pancreatic ducts
-Measles & respiratory infections is more severe w/ deficiency
Vit. D deficiency
Due to:
- limited exposure to sunlight
- impaired fat absorption
- deranged metabolism (liver or kidney disease)
- ↑ fracture risk
- Rickets in children: bowed legs, bossed head, rachitic rosary
- Osteomalacia in adults (↓ mineralization)
- hypocalcemic tetany
- -convulsions
- -Trousseau sign→ spasm w/ BP cuff
- -Chvostok’s sign → mouth, eye muscle contract from tap
Vit E deficiency
Due to:
- fat malabsorption
- abetalipoproteinemia
- ***Low birth weight: immature gut
Neurologic disease
- Spinocerebellar degeneration** (infant)**
- -↓ or absent DTR
- -abnormal eye movements
- -ataxia
- -loss position, vibratory sense, pain sense
Causes for chronic elevations of transaminases
A: α-1 Anti trypsin deficient, AI hepatitis B: HBV C: HCV, Copper (Wilson's disease) D: drugs/herbals E: ethanol F: fat (NASH) H: heart failure I: iron accumulation (hemochromatosis)
Cholestasis, cause & morphology
- Extrahepatic bile duct obstruction
- Intrahepatic bile duct obstruction
- defects in hepatic excretion
- Enlarged hepatocytes w/ bile droplets
- → feathery degeneration
- dilated bile ducts → canaliculi rupture
- Kupffer cells phagocytose bile
At portal tracts:
- ductular proliferation
- edema, bile pigment retention
- surrounding hepatocytes are swollen & degenerating
- leads to ascending cholangitis or biliary cirrhosis
- eventually *PMN inflammation (ascending cholangitis)
- -bile duct epi & lumen
Biliary cirrhosis morphology
Primary– small intrahepatic ducts (predicate inflammation)
Secondary– entire biliary tract
- Intense yellow-green pigmentation
- hard, cirrhotic- finely granular
- dilated bile ducts
- ↑ bile ducts
- feathery degeneration
- periportal mallory-denk bodies
- -periportal fibrosis → jigsaw cirrhotic nodules
Neonatal cholestasis causes
- Idiopathic (50%)
- Biliary atresia (33%)
- Neonatal hepatitis:
- -**α1-AT deficiency
- -Alagille syndrome (paucity of bile ducts)
- -cystic fibrosis
- -infection (syphilis, CMV, sepsis)
- -toxic
vonMeyenburg Complex
Anomaly of the biliary tree
- common
- sporadic inheritance
- bile duct hamartoma
- -prolif. of small ducts adjacent to portal tract
- may be under Glisson’s capsule
Polycystic liver disease
Anomaly of the biliary tree
- fairly common
- auto. dominant
- assoc w. polycystic kidney disease
- multiple cysts in various organs
- -*lined by cuboidal cells
- -straw color fluid
- die of renal failure
Congenital Hepatic fibrosis
Anomaly of the biliary tree
- uncommon
- auto recessive
- assoc. polycystic kidney disease
- *-risk of cholangiocarcinoma
- portal HTN w/o cirrhosis
- curved ducts in fibrous proliferations along septal margins
Caroli disease
Anomaly of the biliary tree
- very uncommon
- auto recessive
- *-risk for cholangiocarcinoma
- segmental dilations of large bile ducts
- -may be assoc. choledocal cysts
- portal HTN
- intrahepatic cholistasis, cholelithiasis
- cholangitis & hepatic abscess
Alagille syndrome
Anomaly of the biliary tree
- uncommon
- auto dominant
- risk of liver failure & HCC
- portal tract bile ducts absent
- → neonatal hepatitis
Budd-Chiari syndrome
- Hepatic vein thrombosis (outflow obstruction)
- -obstruction of 2+ major hepatic veins
- hepatomegaly
- weight gain & ascites
- aminotransferases ↑↑↑ (multi-thousands
- Jaundice
Peliosis hepatitis
impairs blood flow through the liver
-primary dilation of sinusoids
Associated w/:
- anabolic steroids
- rare-oral contraceptives
- usually clinically silent
- -fatal intra-abdominal hemorrhage may occur
Causes of impaired intrahepatic blood flow
- cirrhosis
- sickle cell
- DIC
- -HELLP/eclampsia- fibrin clots in sinusoids
- diffuse intrasinusoidal metastatic carcinoma
- passive congestions due to heart failure
- -centralobular hemorrhagic necrosis
- peliosis hepatitis
Hepatic vein & caval thrombosis
- polycythemia vera
- Inherited thrombophilias
- -pregnancy / postpartum
- -oral contraceptives
- antiphospholipid syndrome
- intra-abdominal cancer (HCC)
Hypercoagulability & sluggish flow
Veno-occlusive disease
Sinusoidal obstruction syndrome
- 1st week after BM transplant (25%)
- hyperbilirubinemia & cholestasis
like budd-chiari but not as severe
- tender hepatomegaly
- ascites
- weight gain
- jaundice
Causes of acute pancreatitis
Metabolic:
- *alcoholism
- hyerlipoproteinemia / hypertriglyceridemia
- **hypercalcemia
- drugs: furosemide
- trypsin mutation (PRSS)
- inhibitors of trypsin (SPINK 1)
- CFTR
Mechanical
- trauma, surgery, ERCP (endscopic)
- obstructed duct
- perforated peptic ulcer
- ischemia
- mumps
Causes of chronic pancreatitis
- Alcohol is most common
- persistent obstruction
- Hereditary
- -PRSS → trypsin mutation
- -SPINK → inhibitor of trypsin
- -CFTR
- Autoimmune → IgG4 plasma cells
Morph:
- fibrosis
- loss of acini
- calcification w/in ducts
- islets spared until late
- hypoalbuminemia
complications of acute pancreatitis
- hypocalcemia
- -shock
- -ARDS
- -acute renal failure
- DIC
- pancreatic abscess
- pancreatic pseudocyst
- duodenal obstruction (ileus ?)
complications of chronic pancreatitis
- pseudocyst
- duct obstruction (calcification)
- malabsorption, steatorrhea
- secondary DM
- pancreatic carcinoma
pancreatic pseudocyst
- develop from necrosis/hemmorhage
- no epithelial lining
- lined by fibrous tissue & granulation tissue
- unilocular
- elevated amylase
- abdominal pain
- mass in region of pancreas
- may hemorrhage, infect, cause peritonitis
Ghrelin
- appetite stimulater
- from arcuate nu. & empty stomach
- stimulates NPY/AgRP neurons (anabolic
- -NPY → NPYR → MCH & orexins
- ↑ food intake
Peptide YY
- satiety signal
- from endocrine cells of ileum; colon
- inhibits NPY/AgRP neurons
- -NPY → NPYR → MCH & orexins
- decreased in Prader Willi
- ↓ food intake
Amylin
- reduces food intake
- from β cells
Leptin
- stimulate POMC/CART (energy use)
- -αMSH → MC4R → TRH & CRH
- inhibits NPY/AgRP (food intake)
- -NPY → NPYR → MCH & orexins
- ↓ food intake
- ↑ energy expenditure
Adiponectin
- ↑ FA oxidation → ↓ fat mass
- insulin sensitizing
- produced by adipocytes
- more in lean individuals than obese
Liver:
- ↓ FA influx
- ↓ TG content
- ↓ glucose production
Muscle:
-directs FA to muscle for oxidation
Complications of obestiy
- Cerebral atherosclerosis
- stroke
- hypoventilation
- pickwickian syndrome (sleep apnea)
- HTN
- LVH
- CHF
- coronary atherosclerosis
- MI
- Non-alcoholic steatosis
- Gallstones
- diabetes mellitus
- renal failure (independent or 2º to diabetes/ HTN)
- dyslipidproteinemia (↑ chol, TG, LDL, ↓ HDL)
- osteoarthritis / gouty arthritis
- reproductive dysfunction
- coagulopathy (DVT & PE)
Osteopathic structural changes of obesity
- Flattened thoracic curve: T3-T5
- ↓ lumbosacral curve
- L5 ant. S1
- sacral extension
- -B/L intermittent lumbar radiculopathy
- -lumbosacral instability
- -constant low back pain
