Assessment 3 Flashcards
Cystinuria
Defect in transport of cystine, lysine, arginine, ornithine
Poor absorption in kidneys/intstines
Cystine accumulates in urine (least soluble)
Treat w/ lots of water
Hartnup disease
Defect in transport of neutral AA (Ile, Leu, phe, Thr, Trp, Val)
Intestine and kidneys
D173N mutation
Lack of tryptophan, treat with try and niacin supplements
Cystinosis
Cannot transport cystine out of lysosome
Autosomal recessive, ESRD by 7-10yrs
Treat with cysteamine - reacts with cystine and end products leave lysosome
Pyruvate TA
Pyruvate –> Alanine
OAA TA
OAA –> Asp
a-KG TA
a-KG –> Glutamate
Alanine to Pyruvate
Transaminations all require…
Vitamin B6
Biosynthesis of Serine
3PG –> Phosphopyruvate –> phosphoserine –> Serine
Glycine synthesis
Serine –> Glycine
Serine hydroxymethyl transferase, creates N5/N10 methylene THF
Most stable THF?
N5 Methyl THF
All THF forms go towards that
Degradative reactions involving THF: Serine
Serine comes from 3PG which comes from Glucose
Glucose carbons —–> end up in THF compound
Degradative reactions involving THF: Formate
Make N10 formyl THF
Degradative reactions involving THF: Histidine degradation
Make N5-formimino THF
Biosynthetic reactions with THF
dUMP to TMP (N5/N10 methylene THF)
Glycine to Serine
Homocysteine –> methionine (N5 Methyl THF)
Purine biosynthesis (N10 formyl THF)
S Adenosylmethionine
Used in all methyl transferase reactions except homocysteine –> methionine
Phe –> Tyr
Enzyme: Phenylalanine hydroxylase
Cofactor: Tetrahydrobiopterin
AA degraded into which 7 families
Acetoacetyl-CoA Acetyl CoA Pyruvate a-KG Succinyl CoA Fumarate Oxaloacetate
Leucine degraded into…
Acetyl CoA
Leucine/Lysine degraded into…
Acetoacetyl-CoA –> Acetyle CoA
AA degradation cycle
Pyruvate –> Acetyl CoA + OAA –> Citrate –> aKG –> Succinyl CoA –> Fumarate –> Oxaloacetate
Ketogenic AA
Leucine
Lysine
Phenylalanine degradation
Phe –> Tyr –> x –> Homogentisic acid –> Fumorylacetoacetate –> Fumarate + Acetoacetate
Alcaptonuria
Buildup of homogentisic acid in urine
Black urine
Arthritis
Phenylketonuria
Cannot breakdown Phe:
Classical - no enzyme
Other - lack of THB
Buildup of TA product phenylpyruvate, phe, phenyllactate
Restrict Phe diet
Tyrosinemia Type I and II
Type I: Lack of fumarylacetoacetate hydrolase
Early death
Type II: Defect in tyrosineaminotransferase, buildup of Tyr
Treat both with low Phe and Tyr diet
Nitisinone
Treatment for Type 1 tyrosinemia
Blocks homogentisic acid production
Bilirubin production
Heme degraded –> biliverdin –> bilirubin –> Attached to albumin –> Carried in blood to liver
Bilirubin in hepatocytes
Albumin released, bilirubin enters hepatocytes –> Conjugated with glucoronic acid, water soluble –> excreted to bile and deconjugated by bacteria in intestines –> most leaves in feces
Hemochromatosis
Defect in HFE gene - excessive iron absorption
Excessive iron accumulation, especially in liver
Autosomal recessive
Hemosiderin (iron storage) deposition = damage to liver, pancreas, heart
Micronodular cirrhosis, diabetes, brown skin
Phlebotomy can be useful treatment
Wilson Disease
Copper accumulation - liver, brain, eye
ATP7B gene mutation (copper transporting ATPase) - Failure to incorporate copper into ceruloplasmin which takes copper to bile
Rare disease
Kayser Fleischer rings (copper in cornea)
Alpha-1 antitrypsin deficiency
Inhibitor of proteases, when not there –> tissue damage
Increase risk for hepatocellular carcinoma
Cirrhosis
Acute fatty liver of pregnancy
Very rare
Microvesicular steatosis
Fetus causes inherited metabolic disorder in mother
Adult Polycystic kidney disease
Mutation in gene encodinc polycystin-1 (transmembrane glycoprotein)
Loss of function of stress response on ciliary membranes = abnormal fluid filled cysts
Familial hypercholesterolemia
Mutation in gene encoding LDL receptor on hepatocytes
Increased blood cholesterol
Heterozygotes have 1/2 LDL receptors, homozygotes have none
Gilbert syndrome
Fluctuating hyperbilirubinemia in response to stress, fasting, exercise
UGT1A1 mutation
Bilirubin conjugator
UGT1A1
Bilirubin transport proteins
Albumin/bilirubin transporter: OATP2
Conjugated bilirubin tranporter: MRP2
Control points for bilirubin clearance
- Uptake
- Conjugation
- Secretion
CAR agonist
Increases bilirubin metabolism and clearance
Unconjugated hyperbilirubinemia
Increased production - hemolysis
Decreased uptake - OATP2
Impaired conjugation
Crigler-Najjar type I vs type II
Type 1: No UGT1A1 activity, high levels of bilirubinemia
Kernicterus
Type II: Reduced UGT1A1 activity, usually benign
Indinavir and UGT1A1
Huge increase in bilirubinemia with Gilbert syndrome
Inhibits UGT1A1
Kernicterus treatment
Expose to light, photoisomerization of Bilirubin
Dubin Johnson Syndrome
MRP2 mutation
Cannot excrete conjugated bilirubin
Black livers - lipofuscin melanin complex
Rotor syndrome
Conjugated bilirubin secreted back into blood (MRP3) cannot be taken back into hepatocyte
OARP1B1/3 defect
Bilirubin and inflammation
Heme oxygenase suppresses inflammation
Activated leukocytes upregulate HO = increased bilirubin = slow inflammation
Neurotransmitters developed from tyrosine
Dopamine
Norepinephrine
Epinephrine
Need B6 and THB
Serotonin
Derived from tryptophan
B6 and THB
GABA
Derived from glutamate
Histamine
Derived from histidine
B6
Homocystinemia/uria
Buildup of homocysteine
Optic lens issues, osteoporosis, mental retardation
B6 can lower levels in 50% of cases (lower affinity of B6 by enzyme)
Defective enzymes that can lead to homocystinemia
- Cystathionine beta synthase (Homocysteine –> Cystathionine)
- N5/N10 methylene THF reductase (N5/N10 methylene THF –> N5 methyl THF)
- Methionine synthase (N5 methyl THF –> THF and Homocysteine –> Methionine)
Elevated homocysteine effects
Decrease endothelial growth
Increase smooth muscle cell proliferation - can exacerbate atherosclerosis
Block coagulation cascade –> clots/thrombosis
Homocysteinemia treatment
Vit supplements: B6, folic acid, B12
Neural tube defects and homocysteine
Does not have direct effect
But can monitor levels of functional folate by checking homocysteine levels
Increased homocysteine = decreased functional folate
Vit B12
Obtain from milk/meat, absorbed via intrinsic factor
Methyl cobalamin: Used Methionine synthase reaction
Adenosyl cobalamin: Methly malonyl coa –> succinyl coa
B12 deficiency - neurological problems
Lack of B12 = lack of methionine = lack of SAM
SAM needed for DNA methylation
Betaine pathway
Choline –> Betaine –> Dimethylglycine
Homocystein –> methionine in final step
Branched chain amino acid metabolism, step 1 and 2
- Transamination, B6 required
2. Branched chain alpha keto acid DH
Isoleucine metabolism final product
Succinyl CoA + Acetyl CoA
Ketogenic and Glucogenic
Leucine metabolism final products
Acetyl CoA
Ketogenic only
Valine metabolism final products
Succinyl CoA
Glucogenic
Maple syrup urine disease
Defect in branched chain alpha keto acid DH
Buildup of branched chain amino acids
Glycine metabolism pathways
- Glycine Serine
- Glycine cleavage enzyme = CO2, N5/N10, NH4
- Oxidase to Glyoxylate, transaminate back to Glycine
Primary Oxaluria type 1
Lack of glycine transaminase
Buildup of Glyoxylate and subsequently oxalate kidney stones
Non ketotic hyperglycinemia
Glycine cleavage enzyme defect
Elevated glycine in CSF and plasma –> Neurological defects because glycine is inhibitory neurotransmitter
Heme synthesis
Succinyl CoA + Glycine –> delta aminolivulenic acid –> x2 –> Porphobiliniogen –> Heme
Lead poisoning
Inhibits heme synthesis
Affects Aminolevulinic acid Dehydratase
Porphyria
Class of defects in heme biosynthesis
Photophobia, eat rare meats
AST/ALT ratio in NAFLD
AST/ALT less than 1
AST/ALT ratio in alcoholic liver disease
AST/ALT >1
NASH vs hepatic steatosis
NASH has fibrosis, not to extent of cirrhosis
Hepatic steatosis has fatty droplets only
Ballooning degeneration
NASH
Cells swell and fill with fluid, nuclei in center
Cirrhosis
Extensive fibrosis around regenerating nodules
Large web of fibrosis and noticeable cell damage
Collagen deposition in Space of Disse = blockage of hepatocytes to blood
Mechanisms of death in cirrhosis
Liver failure
Portal hypertension
Hepatocellular carcinoma
Alcoholic liver disease
Cirrhosis preceded by hepatic steatosis and alcoholic hepatitis
Mallory bodies surrounding hepatocytes
Alcohol metabolizing enzymes create more NADH and H = more lipid synthesis = fatty droplets
Hyperdynamic circulation
Portal hypertension = body response to dilate arteries = BP Drop = more salt/water retained = even more edema
Ascites
Fluid in peritoneal cavity
Hypoalbuminemia, hyperdynamic circulation
NAFLD
Due to hyperlipidemia, obesity etc
Steatosis more common than NASH
NAFLD lab findings
AST/ALT
NAFLD guidelines
Weight loss reduced hepatic steatosis
Loss of body weight helps steatosis but need more for necroinflammation improvement
Exercise may help
NASH treatment?
Vitamin E
Intrahepatic cholestasis vs extrahepatic
Intrahepatic: Defective bile secretion or intrahepatic bile duct disease
Extrahepatic: Mechanical obstruction or injury of large bile ducts outside of liver
Cholestasis clinical features
Jaundice
Pruritis
Malabsorption
Cholestasis lab findings
Elevated ALP, GGT, 5NT
Elevated conjugated bilirubin
Secondary biliary cirrhosis
Prolonged obstruction of extrahepatic biliary tree
Fibrosis of liver –> cirrhosis
Intrahepatic cholestasis histology
Centrilolobular
Intracellular and canalicular
Hepatocyte necrosis
Extrahepatic cholestasis histology
Bile duct/bile plugs
Edema and acute inflammation of portal tracts
Cholelithiasis
Gall stones
Can be asymptomatic
Cholesterol (80%) and pigment stones
4 F’s of gall stones
Female
Forties
Fat
Fertile
Biliary colic
Severe RUQ pain post prandial
Fatty food intolerance
Acute cholesytitis
Murphys sign
Palpable gall bladder
Elevated ALP and leukocytosis
Acute cholecystitis complications
Gangrenous cholecystitis
Emphysematous
Stone in bile duct
Gall bladder hydrops
Acute cholecystitis treatment
Early cholestectomy
Intraoperative cholangiogram to rule out common bile duct stones
Electrolytes/fluid
Choledocolithiasis
Stones in biliary tree
Obstruction can lead to ascending cholangitis - bacterial infection of bile ducts
Acute Cholangitis
Bacterial infection of biliary tree
Inflammation aggravated
E. coli, Clostriidium, Enterobacter
Charcot triad
Abdominal pain, fever, jaundice
Reynolds Pentad
Charcot triad + hypotension, altered menta status
Clinical features of acute cholangitis
Charcot triad
Reynolds Pentad
Elevated WBC
Acute pancreatitis
Can be caused by stone in Ampulla of Vater, occlusion of pancreatic duct
Acute pancreatitis clinical
Elevated amylase/lipase
Hypocalcemia
Leukocytosis
Biliary atresia
Luminal obstruction of biliary tree
Congenital
Biliary atresia treatment
Kasai portoenterostomy
Liver transplant
Primary sclerosing cholangitis
Cholestatic liver with fibrosis and inflammation
Narrowing/obstruction of larger bile ducts –> cirrhosis
Males>females
70-75% coexisting IBD
PSC ERCP
segmental constrictions
String of beads
PSC clinical/lab features
Fatigue, pruritis, jaundice
Antinuclear antiboy
Anti smooth muscle anti body
p-ANCA
PSC cirrhotic stage
Biliary cirrhosis
3-6 years after presentation
Cholangiocarcinoma
Rare
PSC is risk factor
Poor prognosis
Painless jaundice, clay stool, cola urine
Obstructive jaundice labs (GGT, ALP, Bilirubin increase)
Courvoisier Sign
Jaundice + Palpable gall bladder
Painless jaundice
Primary biliary cirrhosis
Granulomatous destruction of intrahepatic bile ducts
Female>Male
Hepatocellular carcinoma risk
Pruritis, fatigue, jaundice (late)
Can be asymptomatic
PBC treatment
Ursodeoxycholic acid
Cholestyramine - bind bile salts in intestines to enhance excretion
Immunosuppressants
liver transplant
Autoimmune hepatitis
Female predominance
Immune system attacks hepatocytes
High IgG and gama globulin
Liver biopsy
Prednisone, azathioprine
Autoimmune hepatitis Type 1
More common, all ages
Antinuclear antibody
Anti smooth muscle antibody
Anti actin antibody
Autoimmune hepatitis type 2
Girls and women, children 2-14
Anti livery kidney microssome
Anti liver cytosol-1
Most common HIV transmission
Male to male sexual contact
5 body fluids that transmit HIV
Blood Semen/pre semen Rectal secretions Vaginal secretions Breast milk
HIV Transmission types (3)
Sexual (horizontal transmission)
Blood exposure: Needles, IV drug use, transfusions
Vertical transmission: Fetus in birth canal or in utero, breast milk
Postive male/Negative female prevention
Donor insemination
Sperm washing
IVF w/intracytoplasmic sperm injection
Positive female/Negative male prevention
Intra-uterine insemination
IVF
HIV risk by type of exposure: Sexual
Least risk Insertive vaginal Receptive vaginal Insertive anal Receptive anal Highest risk
HIV risk by type of exposure: Blood exposure
Least risk Needle share Needle stick Mucous membrane exposure Transfusion Most risk
Best HIV diagnosis
HIV Ag/Ab test + Ab differentiation test
Earlier diagnosis
Newborn HIV test
Newborns carry maternal Ab
HIV RNA quantitation at different time frames
AZT for 6weeks
Acute HIV infection
2-6 weeks after exposure
- Mono like illness, adenopathy and pharyngitis
- Rash on trunk
- Neurological symptoms
HIV infection: first 3 months
Huge rise in viral count, decline in CD4 count
HIV immune response occurs and viral load decreased to steady state level
HIV monitoring
Viral load
CD4 cell count
Steps of HIV progression
- Binding/Fusion
- Uncoating
- Reverse transcription
- Integration
- Proviral transcription
- Translation
- Cleavage
- Assembly, maturation, release
Binding and Fusion drugs
CCR5 antagonist
Fusion inhibitor: Enfuviritide - side effect, injected, no bueno
Uncoating
Virus fused with CD4 membrane, viral RNA released into cytoplasm
Reverse Transcription
Viral RNA transcribed into DNA
Reverse transcription drug classes
NNRTI: Prevents binding of RT to HIV RNA
NRTI: Allows RT and HIV RNA binding, chain terminator, eventually DNA degrades
NNRTI drugs
Efavirenz - dreams
Rilpivirine - Need food
Entravirine: CYP450
NRTI drugs
Zidovudine - AZT, children born to HIV+ mothers
Lamivudine (3TC) - Hep B
Emtricitabine (FTC) - Hep B
Abacavir - Hypersensitivity, HLAB5701
Tenofovir (TDF/TAF) - decreased bone density, renal toxicity
Integration drugs
-tegravir
Raltegravir - Rash, myopathy
Elvitegravir
Dolutegravir - hypersensitivity
Proviral transcription
Viral DNA reprograms CD4 machinery to produce Viral RNA and viral mRNA
Translation
Ribosomes use viral mRNA to create proteins/enzymes in polyprotein
Cleavage
Proteases cut polyprotein and release enzymes/proteins needed for creation of new HIV virus
Protease inhibitors
Ritonavir (RTV): First PI, used as booster
Lopinavir (LPV): Increase cholesterol/TG
Darunavir (DRV): Hypersensitivity
Atazanavir (ATV): Kidney stones, UGT1A1 inhibitor
HIV clearance evasion
Rapid replication
Mutagenesis
Latency
Down regulation of MHC on infected cells
Structure
Infection of sanctuary sites
Chronic HIV infection
Latency phase, generally asymptomatic
Immune system able to limit replication, virus lays dormant
Avg 8-10 years
Immune defects in HIV+
Low CD4
Dysregulation: altered cytokines, impaired response to antigens, hypergammaglobulinemia
When to start ART
All HIV patients, differs based on baseline CD4 levels
Absolute indications for ART
Hep B/C HIV associated neuropathy HIV associated neurocognitive disorders Pregnancy Malignancy AIDS defining disease
ART start: 3 medications
2 NRTI + integrase inhibitor OR protease inhibitor
Morphological changes with ART
Lipodystrophy
Lipohypertrophy
Lipoatrophy
HIV mutagenesis
Mutation rate of 1/10,000
Mutation occurs during Reverse Transcription
CD4 response after ART
Increased numbers Response to non HIV antigens Decreased inflammatory cytokines No response to HIV antigens Response to new antigens
AIDS definition
CD4
Candidiasis
Oral thrush
CD4
PCP/PJP
Pneumocystits iroveci (carinii) Pneumonia
CD4
Cryptococcal Meningitis
CD4100 for 3mo, undetectable, start ART
Toxoplasmosis
CD4
Mycobacterium Avium
CD4
AIDS defining cancers
Kaposi Sarcoma
Non hodgkins lymphoma: EBV
Cancer of cervix/anus/rectum: HPV
Biochemical nutritional evaluation
Albumin
Transferrin
Prealbumin
Retinol binding protein
Pregnancy nutrition
Energy: +340 2nd tri, +450 3rd tri
Protein +25
Carbs
Iron +50%
Folate +50%, B12
Food to avoid during pregnancy
Vit/mineral mega doses
Fish w/mercury
Soft cheeses/food poisoning risks
Lactation nutrient needs
+500 kcal energy
All more than during pregnancy, nutrient dense foods
Inadequate diet = reduced milk quantity and deprives mother of nutrient stores
Infancy nutrients
Energy and protein highest/kg in infancy
30g fat
Vit/minerals highest than during adulthood
Infancy food guidelines
Solid foods @4-6 months
Introduce foods singly at intervals, 3-5 days
Iron rich/vit C
Childhood nutrients
Energy need increases, but per kg decreases
Carb: Fiber = age +5
High quality protein
Fat: 30-40% 1-3yrs
25-35% 4-18
Nutrient concerns in childhood
Iron
Vit D: Fortified milk/cereal
Fluoride: Water
Adolescence
Puberty/growth spurt
Tanner staging
Energy, protein, vit/mineral increase
Acute Liver Failure Definition
Coagulation abnormality, mental alteration
No preexisting cirrhosis
Illness less than 26 weeks
Acute liver failure stats
2000 cases anually
33% mortality, 40% survival without transplant
> 65% survival with transplant
ALF etiology
Mainly drugs, esp acetaminophen
Hep A/B
Unknown
ALF classification
Hyperacute: 7d
Acute: 8-28d
Subacute: 29-60d
ALF type and cause
Subacute: Drug
Acute: Acetaminophen, Hep A
Acute: Hep B
Acetaminophen toxicity
Enhanced P450 –> NAPQI toxicity
Doses >15g
Hepatic dysfunction at day 3
Acetaminophen overdose treatment
Glutathione precursors
Hep B ALF
1% pt with Hep B, 8% ALF is HBV
.4% mortality
Hep A ALF
Less than 1% Hep A pts
Elevated creatinine
ALF complications
Jaundice Infection Hepatic encephalopathy Coagulopathy Metabolism issue Renal failure
Hepatic encephalopathy treatment
Airway protection
Lactulose - meh
Sedation
Coagulopathy
Decreased synthesis of clotting factors
Decreased platelets
Infection and ALF
80-90%
Sepsis is leading cause of death
G+
Phase I enzymes
Minor structural changes, oxidation
CYP
Phase II enzymes
Large molecular additions
Transferases: UGT
CYP3A4
Most common CYP used by many drugs
CYP2D6
Neurological drugs
Genetic polymorphism
Rifampicin
Most important CYP3A4 inducer
Results in other drug concentration reduction
Most powerful CYP competitive inhibitor
Ketoconazole
Huge increase for other drug
Hepatitis A Virus
Single serotype
Acute disease, no chronic infection
Usually asymptomatic
Lifelong immunity after immune response
Hep A transmission
Fecal oral
Personal contact
Blood exposure (RARE)
Hep A pathogenesis
Survives in stomach and enters blood –> liver
Replicates in hepatocytes, not cytotoxic
Excreted in stool before jaundice
Immune mediated damage to liver
Hep A clinical features: Incubation, symptoms
Avg incubation: 28-30 days
Cholestasis, dark urine, clay stool, jaundice
Jaundice more likely as age increases
Hep A antibody history
IgM detectable 5-10 days before symptoms
IgG 4 weeks post infection then mass rise
Hep A diagnosis
Serum HAV IgM antibody
Hep A prevention
Hygiene
Sanitation
Vaccination: Recombinant (pre), Immune globulin (post)
Hep E
Acute asymptomatic in developing countries
Enteric zoonotic transmission
Very rare in developed countries
HEV pathogenesis
15-60 day incubation
Replication in hepatocytes, feces excretion
Ab pain, anorexia, fever, hepatomegaly, jaundice
HEV natural history (Ig and enzymes)
Large ALT rise at around 6 weeks post infection
IgM rise faster than IgG
HEV mortality
Relatively low but 20% in pregnant women
HEV diagnosis/prevention
Antibody assays available but inconsistent
anti HEV IgG/IgM
HEV RNA detection
No antivirals
HEP B
DNA virus with RNA intermediate
350mil infected
Multiple genotypes with differing progression/response rates
HBV transmission
Blood, semen, vaginal
HBV pathogenesis
Multiple viral proteins: Surface, core, E, Polymerase, X
Detectable protein is HBsAG (surface)
Not cytotoxic, immune mediated damage
HBV pathogenesis
2-3 month incubation
Jaundice
Low acute case mortality
15-25% chronic case fatality
HBV diagnosis
Choestasis
AST/ALT elevation
IgM anti HBsAg = acute infection
HBsAg+ = infectious
HBeAg correlates with infectiousness
Acute HBV natural history: Virus, enzymes, Ag, Ig
Large rise of virus within weeks = large rise in antigen, decline at 3mo
IgM anti HBc at clinical onset then declines @6months
Anti HBsAg = resolution of disease, viral load/Ag undetectable
Chronic HBV natural history
Large rise in DNA/HBsAg
Antigen persists = chronic
IgG HBc rises and persists
IgM anti HBc decrease = chronic
Immunity with HBV vaccination serology
HBsAg = negative anti-HBc = negative anti-HBs = positive
Immunity with HBV infection serology
HBsAg = negative
anti HBc = positive
anti HBs = positive
Chronic HBV infection serology
HBsAg = positive
Anti HBc = positive
Anti HBs = negative
IgM anti HBc = negative
Acute HBV infection serology
HBsAg = positive
Anti HBc = positive
anti HBs = positive
IgM anti HBs = negative, rises after resolution of disease
HBV prevention/treatment
Vaccine: HepB IG, Recombinant
Treatment: IFN
Polymerase inhibitors - Lamivudine, Tenofivir, Emtricitabine
Hep C
Leading cause of liver transplant
RNA virus
Hep C transmission
IV drugs
Transfusion/transplantation
Sexual and perinatal but much lower than HBV
HCV natural history
Exposure (20% resolved)
Chronic (Some stable/variable progression)
Cirrhosis (Some slowly progressive)
HCC/Transplant/Death - 25yrs
HCV diagnosis
HCV antibody - Not good early/acute
HCV RNA - Better
Abnormal liver enzymes
Acute HCV natural history
Large ALT rise with HCV RNA detection
Huge anti HCV after a few months
Chronic HCV progression
HCV RNA detection
Large initial ALT rise, then decline, then variable spikes
Anti HCV increase like in acute
HCV vaccine
NONE
Sofosbuvir
2014: NS5B polymerase inhibitor
Boceprevir/Telaprevir
NS3/4A protease inhibitors
Hep D
HBV coinfection
Derived from HBV
Cytotoxic effect on hepatocytes
No bueno
Hep D detection
Anti HD Ab detected via ELISA
HBV vaccination protects from HDV
HBV antivirals DO NOT reduce HDV
ALF and urea
Liver can’t create urea so ammonia leaves and goes to brain
Ammonia becomes glutamate, osmotic pressure increase –> increase intra cranial pressure
NAS scoring system categories
Steatosis
Lobular inflammation
Ballooning degeneration
Fibrosis
ALF liver transplant contraindications
Uncontrolled intracranial hypertension
Prolonged systemic hypotension
Sepsis/ARDS
Lab parameters for liver transplant
Creatinine
INR
Total Bilirubin
Achilles heel of liver transplantation
Biliary complication
Bile leaks/obstruction/strictures
Porcelain gall bladder
Wall thickening and calcium deposition
Increased risk of gall bladder carcinoma
PSC treatment
Endoscopic balloon dilation
Endoscopic stent
Liver transplant
PSC histology (Stain and presentation)
Trichrome stain
Onion skin fibrosis
Klatskin Tumor
Cholangiocarcinoma arising at hepatic hilum
No gall bladder distention
PBC Lab findings
Antimitochondrial antibodies
Increased IgM
Elevated ALP but NORMAL total bilirubin
Cirrhosis - 3 morphological characteristics
- Bridging fibrous septa
- Regenerative parenchymal nodules
- Architectural disruption throughout entire liver
Hepatic stellate cells
When activated, deposit collagen into Space of Disse
Intra/pre/post hepatic portal hypertension
Intra: Cirrhosis
Pre: Portal vein thrombosis
Post: Hepatic vein thrombosis
Clinical consequences of Portal Hypertension
Congestive Splenomegaly
Hepatic Encephalopathy
Portosystemic venous shunts with risk of bleeds
Ascites
Chronic liver disease signs
Caput medusae (PH)
Jaundice/Scleral icterus (Hyperbilirubinemia)
Asterixis (flapping tremor)
Encephalopathy (Ammonia)
Gynecomastia/spider angiomas (Androgen/estrogen metabolic dysfunction)
Palmar erythema (Red palms)
Ultrasound benefits
Bile duct dilation
Gall bladder
Hepatic vasculature
Obese patients ruin everything
CT benefits
Optimal with contrast
Visualize ductal dilation
Better assessment of pancreas and level of obstruction
Gall stones can’t be seen though
MRI benefits and contraindications
Evaluate hepatic parenchyma
Level and etiology of obstruction
Biliary and pancreatic ducts via MRCP
Contraindications: Pacemakers, obesity
Nuclear Medicine
Functional assessment of biliary system
Sensitive to diagnosis of acute cholecystitis
Iminodiactetic acid analogues
Nuclear medicine technique
Uptake by hepatocyte, transport into bile canaliculi, excreted into biliary system
Flows into gall bladder
Endoscopy
ERCP: Direct access to papillae, can extract stones or place stents
PTC
Percutaneous Transhepatic Cholangiography
Access biliary system through skin/liver
Dilate/stent strictures
Neonatal jaundice TORCH
Etiologies
Toxoplasmosis Other Rubella CMV Herpes
Ascending Cholangitis bacteria
E Coli
Enterococcus faecalis
Klebsiella Pneumoniae
Ascending because bacteria starts in intestines then moves up bile duct to liver
Entamoeba Histolytica
Ingest cysts, trophozoites burrow into intestines, can get into liver
Anchovy paste nastiness
Liver abscesses
Treat with Metronidazole
Physiological jaundice of newborn
Takes time for baby to start conjugating bilirubin
High levels dangerous, goes to brain = kernicterus
Simple cyst
Thought to be congenital
Common - 5%
Liver abscess - pyogenic
Induce pus formation
E. Coli
Klebisella pneumoniae
Strep
Bacteroides
Drain
Metronidazole, clindamycin
3rd gen cephalosporin
Hydatid Cyst
Echinococcus granulosis - tapeworm (cestode)
Live in intestinal lumen (definitive host), Tissue cysts (intermediate hosts)
Humans are accidental hosts
Liver and lungs
Surgery, albendazole (blok glu uptake)
Ascariasis
Nematode - roundworm
Common infestation
Travel up lungs and into GI tract and grows –> to liver causing abscesses
Mebendazole
Fasciolasis
Liver flukes - flatworms
Watercress salad
Schistosoma
Swimmers itch
Katayama fever
Eggs in liver = granulomatous reaction, fibrosis, portal hypertension
Eosinophilia
Risk of hepatocellular carcinoma