Term
Jaundice:
yellow discoloration of scleras and skin
darkening of the urine
inability of liver cells to conjugate and excrete bilirubin leads to build up of bilirubin in the blood |
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Definition
| pathophysiology of jaundice secondary to cirrhosis |
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Term
Portal HTN: increased gradient between the portal venous and central venous pressure (inferior vena cava)
hepatocellular injury grogresses -> fibrous material develops within the hepatic lobules -> desrupts normal blood flow through the liver
fibrous tissue accumulates -> resistance to portal blood flow increases -> persistent and progressive elevations in portal blood pressure
also increases in endothelin (vasoconstrictor) and decreases in nitric oxide (vasocilator) attenuate increases in portal venous pressure |
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Definition
| pathophysiology of portal HTN secondary to cirrhosis |
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Term
varices:
portal-to-systemic shunting -> alternative routes of blood flow fromt he portal system to the systemic circulation
deoxygenated blood goes around the liver b/c the portal vein is blocked
blood "backs up" from portal HTN and finds an alternative route back to the systemic circulation
varices decompress the portal system and return blood to the systemic ciculation
varices can occur at any level of the GI tract
most clinically significant route is the gastric vein and development of esophageal varices
risk of variceal bleeding begins when portal venous pressure reaches 12 mmHg > inferior vena cava pressure |
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Definition
| pathophysiology of varices secondary to cirrhosis |
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Term
rupture of varices into the GI tract leading to blood loss -> can progress to hypovolemic shock
hemorrhage is complicated by the hypocoaguable state that accompanies liver disease |
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Definition
| pathophysiology of acute variceal hemorrhage secondary to cirrhosis |
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Term
ascites: pathological accumulation of lymph fluid within the peritoneal cavity
earliest and most common presentation of cirrhosis
portal HTN coupled with arterial vasodilation (compensation for increased pressure in the poral vein) and Na/water retention via activation of the renin-angiotensin system (body thinks it is hypotensive b/c of arterial vasodilation and activates RAAS) -> plasma volume expansion -> translocation of lymph fluid from the hepatic sinusoids and splanchnic capillaries into the peritoneal cavity |
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Definition
| pathophysiology of ascites secondary to cirrhosis |
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Term
SBP: infection of ascetic fluid in absence of primary intra-abdominal source of infection
overall not well understood - likely result from seeding of ascetic fluid via blood, lymph, or bacteria crossing GI tract wall
most common pathogen = gram-negative enterobacteriaceae, especially E. coli |
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Definition
| pathophysiology of spontaneous bacterial peritonitis |
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Term
HE: neuropsychiatric syndrome with broad spectrum of neurological impairment; waxing and waning alterations in mental status that occurs as a consequence of hepatic failure or portal-to-systemic shunting
accumulation of gut-derived nitrogenous substances (specifically ammonia) bypass the liver via portal-to-systemic shunting -> enter the CNS and alter neurotransmission
elevated arterial ammnoia levels are the most commonly cited causative agent although there is poor correlation with ammonia levels and severity of HE
clinical symptoms range from subtle mental status changes to deep coma
can progress over any time period (hours to days) |
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Definition
| pathophysiology of hepatic encephalopathy |
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Term
reduced synthesis of clotting factors
decrease absorption of vitamin K
vitamin K activated clotting factors II, VII, IX, and X |
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Definition
| pathophysiology of coagulopathy secondary to cirrhosis |
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Term
yellow discoloration of scleras and skin
darkening of the urine |
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Definition
| clinical manifestations of jaundice |
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Term
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Definition
| clinical manifestations of portan HTN |
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Term
upper GI bleed - variceal hemorrhage
hemorrhoids
caput medusa - on the abdomen, veins branch out (like medusa) on the surface of the skin |
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Definition
| clinical manifestations of varices |
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Term
hematemesis or melena
decrease ini hemoglobin (Hgb) or hematocrit (Hct)
possible hypotension, dizziness |
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Definition
| clinical manifestations of acute variceal hemorrhage |
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Term
serum ascites albumin gradient (SAG):
determines if ascites is result of portal HTN
requires diagnostic paracentesis (stick needle into peritoneal space, look at albumin level in the serum and in the peritoneal space)
SAG = serum albumin - ascetic albumin
if SAG > 1.1 g/dL = portal HTN present with 97% accuracy
clinical manifestations:
increased abdominal girth
fluid wave
shifting dullness
shortness of breath
hyponatremia - extra water being retained causes hyponatremia |
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Definition
| clinical manifestations of ascites |
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Term
fever
increased WBC count (leukocytosis)
abdominal pain
gaurding
hypoactive/absent bowel sounds
rebound tenderness
SOME PATIENTS ASYMPTOMATIC |
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Definition
| clinical manifestations of spontaneous bacterial peritonitis (SBP) |
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Term
cognitive changes:
confusion (ranging from mild to severe)
agitation
euphoria
restlessness, insomnia
reversal of day/night sleep pattern
somnolence, coma
motor changes:
fine tremor
slowed coordination
asterixis - patients hold up hands; most people can do this steadily; people with HE will flap their hands
posturing and flaccidity
increased serum ammonia levels |
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Definition
| clinical manifestations of hepatic encephalopathy |
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Term
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Definition
| clinical manifestations of coagulopathy |
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Term
low protein levels in the ascetic fluid (< 1 g/dL)
high bilirubin (2.5 mg/dL)
variceal hemorrhage
prior SBP |
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Definition
| risk factors for development of SBP |
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Term
low ascetic protein levels (< 1 g/dL)
variceal hemorrhage |
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Definition
| indications for primary prophylaxis for SBP |
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Term
| previous SBP, prophylaxis is lifelong |
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Definition
| indications for secondary prophylaxis for SBP |
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Term
GI bleed
infection
excessive dietary protein intake
constipation
electrolyte abnormalities
electrolyte abnormalities
azotemia/dehydration/overdiuresis
sedative medications
non-compliance
portosystemic shunts
acute or chronic liver failure |
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Definition
| precipitating factors for hepatic encephalopathy |
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Term
NON-SELECTIVE BETA BLOCKER = FIRST LINE
mechanism:
inhibit beta1 and beta2 receptors and allows unopposed alpha1 vasoconstriction
beta1 receptor inhibition leads to a decrease in cardiac output and beta2 receptor inhibition decreases splanchnic blood flow
the combined effects produce a decreased portal pressure
agents and dosing:
PROPRANOLOL 10 mg po tid
NADOLOL 20 mg po daily
titrate doses to decrease in resting HR or ~25%, an absolute HR or 55-60 bpm, or development of ADRs
NITRATES
mechanism:
smooth muscle vasodilation -> decrease portal pressure
place in therapy:
as ADD-ON THERAPY to patients that have inadequate response to beta blockers as monotherapy
agents and dosing:
isosorbide mononitrate 20 mg po bid
titrated to 20 mg po tid after 1 week if tolerated |
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Definition
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Term
ENDOSCOPIC BAND LIGATION (EBL)
place in therapy:
for patients with contraindications or intolerance to non-selective beta blockers
***superior to both beta blockers and nitrates for preventing first bleed - BUT since not proven to improve survival and long term benefits are still uncertain, therapy is reserved for those intolerant to beta-blockade***
mechanism:
draw in veins and snap on rubber band; cuts off circulation to abnormal veins and reduces risk of future bleeds; areas that are banded slough off |
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Definition
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Term
supportive measures
vasoactive therapy
antibiotics
endoscopic interventions
surgical interventions |
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Definition
| treatmet of acute variceal hemorrhage |
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Term
adequate fluid resuscitation - PRBCs, crystalloids
monitor for presentation or progression to hypovolemic shock
correction of coagulopathies and thrombocytopenia
fresh frozen plasma (FFP), platelets, vitamin K |
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Definition
| supportive measures for an acute variceal hemorrhage |
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Term
smoatostatin, OCTREOTIDE, vasopressin (ADH), terlipressin
OCTREOTIDE = preferred agent
mechanism: naturally occurring somatostatin analog; inhibits vasoactive intestinal peptide -> mesenteric vasoconstriction -> decreased splanchnic blood flow -> decreasing portal and variceal pressure
ADRs: bradycardia, hyperglycemia, GI disturbances
other vasoactive therapies:
vasopressin - non-selective vasoconstrictor witn the vasoconstricting effects not restricted to the splanchnic vessel; ADRS - coronary ischemia, AMI, arrhythmias
terlipressin - analog of vasopressin with longer half-life; allows for q4h dosing rather than continuous infusion; not available in the US; drug of choice in Europe |
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Definition
| vasoactive therapy for acute variceal hemorrhage |
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Term
place in therapy:
ALL PATIENTS WITH A VARICEAL HEMORRHAGE SHOULD BE ON ANTIBIOTICS
active bleeding places patients at high risk of infection
increased risk due to:
aspiration
placement of multiple IV access devices
sclerotherapy
translocation
defects in immune function
ANTIBIOTICS REDUCE THE RISK OF SEPSIS -> REDUCES THE RISK OF REBLEEDING AND INCREASE SHORT-TERM SURVIVAL
screen for infection (spontaneous bacterial peritonitis) |
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Definition
| Antibiotics use in acute variceal hemorrhage |
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Term
place in therapy:
guidelines recommend as PRIMARY DIAGNOSTIC AND TREATMENT STRATEGY for upper GI tract hemorrhage secondary to portal HTN and varices
sclerotherapy:
inject EPI into varices causing vasoconstriction and decreased blood flow to the area
band ligation:
placement of rubber bands around each varix
after placement the varix will slough off after 48-72 hours |
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Definition
| endoscopic interventions for an acute variceal hemorrhage |
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Term
place in therapy:
if standard therapy fails (salvage)
transjugular intrahepatic portosystemic shunt (TIPS):
placement of one or more stents between the hepatic vein and portal vein
DECOMPRESSES PORTAL SYSTEM BY SHUNTING BLOOD AROUDN THE LIVER
complications of TIPS:
hepatic encephalopathy (ammonia would normally be broken down by the liver, but is being shunted away and goes to the brain causing encephalopathy)
shunt malfunction |
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Definition
| surgical interventions for an acute variceal hemorrhage |
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Term
any of below alone or in combination:
endoscopic management:
endoscopic band ligation (EBL) or endoscopic injection sclerotherapy (EIS) q 2 weeks until varices are gone, then re-endoscope at 3 and 6 months
non-selective beta blockers
non selective beta blockers + nitrates
TIPS procedure |
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Definition
| secondary prophylaxis against an acute variceal hemorrhage |
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Term
therapeutic paracentesis:
if tense ascites is present - 4-6 L removal of ascetic fluid prior to institution of diuretic therapy
sodium restriction:
diuretics:
slow diuresis - max daily weight loss of 0.5 kg/day to avoid hypotension
agents and dosing - SPIRONOLACTONE 100 MG DAILY + FUROSEMIDE 40 MG DAILY
rationale for combo - spironolactone has ~14 day delay in onset of action
titrate diuretic using 100mg:40mg ratio up to max combo dose of 400 mg spironolactone:160 mg furosemide
rationale for ration = usually maintains normokalemia
diagnostic paracentesis:
much smaller volume that therapeutic paracentesis
rule-out spontaneous bacterial peritontitis
determine if ascites is a result of portal HTN (SAG) |
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Definition
| initial treatment of ascites |
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Term
serial, therapeutic paracentesis:
on PRN or scheduled basis
albumin infusion post paracentesis is recommended if > 5 L removed
give 8-10 g of albumin for every L of fluid removed above 5 L to replace oncotic pressure |
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Definition
| refractory treatment of ascites |
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Term
ANTIBIOTICS + ALBUMIN
antibiotic therapy:
3rd generation cephalosporin - cefotaxime 2 g IV q8h; ceftriaxone 2 g IV q24h
fluoroquinolones - ciprofloxacin 400 mg IV q12h or 500 mg po bid; levofloxacin 750 mg PO/IV q24h
duration of therapy - 5 days if repeat paracentesis at 48 hours reveals sterile ascetic fluid; 10-14 days if no follow up paracentesis performed; primary prophylaxis (for variceal bleed) x 7 days
albumin therapy |
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Definition
| primary prophylaxis and treatment of spontaneous bacterial peritonitits |
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Term
SMX/TMP 800/160 mg po bid
ciprofloxacin 750 mg po q week
DURATION OF TREATMENT IS LIFELONG, ONCE THE PATIENT HAS HAD SBP
concerns:
development of resistant organisms
fungal infections |
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Definition
| secondary prophylaxis for spontaneous bacterial peritonitis |
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Term
treat underlying and/or precipitating factors - KEY
avoid and/or discontinue CNS depressants
avoid loop diuretics -> hypovolemia can aggravate problems
dietary protein management
pharmacological - aimed at decreasing ammonia production
INTESTINAL CLEANSING
ANTIBACTERIALS |
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Definition
| treatment of hepatic encephalopathy |
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Term
LACTULOSE = FIRST LINE
mechanism:
remove nitrogen containing compounds from the GI tract
lower GI pH -> bacteriostatic effect reduces number of ammonia-producing bacteria
decreases ammonia content in GI tract leading to diffusion of additional ammonia into the GI tract from serum and then subsequent GI removal
dose:
acute - start with 30-60 ml/dose q2h until catharsis begins then scedule 15-30 ml po qid - titrated to produce 2-4 soft stool per day
acute with no PO access - retention enema of 300 ml lactulose in 700 ml water or NS - held for 30-60 minutes
chronic - most patients require 30-60 ml per day - titrate to 2-4 stools/day |
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Definition
| agents used for intestinal cleansing in hepatic encephalopathy |
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Term
mechanism:
inhibit activity of urea producing bacteria
place in therapy:
patients refractory to lactulose
can use in combo with lactulose or substitution
agents:
neomycin - ADRs ototoxicity and nephrotoxicity
metronidazole - ADRs GI, metallic taste, disulfram-like reaction with alcohol intake
rifaximin - ADRs GI |
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Definition
| antibacterials used for hepatic encephalopathy |
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Term
vitamin K IV/SQ/PO daily for 3-5 days
fresh frozen plasma (FFP) for prolongation of PT/INR - give if patient is actively bleeding or before invasive procedure to decrease bleeding |
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Definition
| treatment of coagulopathy |
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