Week 13: Acute Hepatic Dysfunction Flashcards
what 3 criteria are found when a pt. has acute liver failure?
coagulopathy with an INR greater than 1.5
mental status change
loss of hepatic function
liver functions
- regulates most of chemical levels in blood
- excretes bile which helps carry away toxins
- break down of fat
- conversion of glycogen that can be used later for glucosea as energy (glycogen stored in live)
- regulation of many amino acids
- helps iron be incorporated into hemoglobin
- converts amonia to urea
liver enzymes
- Alanine transaminase (ALT)(specific to liver itself): normal 5-35 U/mL, Increase 20X normal range trend in liver disease
- alt/ast ratio greater than 1: related to alcohol induces cirrohsis
- alt/ast less than 1: acute hepatitis
- aspartate aminotransferase (AST) (not specific to liver): normal 0-35 U/L, increased levels trend in liver disease
- Alkaline Phosphatase (ALK Phos): normal 20-90 U/L, 2-3X increase with bile obstruction trend in liver disease
isoenzymes
- lactate dehydrogenase (LDH): (Liver or muscle damage), LDH4- 8-16, LDH5- 6-16
- alkaline phosphatase isoenzymes (5-N) (hepatobiliary tissue), Less than 17 U/L
- Gamma-glutamyl transpeptidase (GGT)(hepatobiliary, renal, and pancreatic tissues): 0-45 U/L
*make sure pt. is fasting before we draw these
bilirubin
- total:0.1- 1.2 mg/dL
- direct:0.1- 1.0 mg/dL
- indirect:0.1- 0.3 mg/dL
- urobilirubin:Negative in fresh void urine
- Jaundice when total bili levels above 2.5
Coagulation studies
Liver produces
- Prothrombin
- Vitamin K
- Help control the bleeding times
- will see increased bleeding times
the higher the PT, the greater extend of liver damage. Very prognostic
Partial Thromboplastin Time (PTT): Measures intrensic coagulation pathway
Prothrombin Time (PT): measure extrinsic coagulation pathways
Three causes of anemia in liver disease
- potential blood loss
- liver not properly forming RBC’s
- excessive distruction of the RBC’s
Serum ammonia
- Normal range 15-45 mcg/dL
- Elevation indicates liver not converting ammonia to urea
- Arterial levels a better indicator of true amonia levels
Serum albumin
- Normal range 3.5- 5.0 g/dL
- Synthesized by the liver
- Decreases in liver disease
- Poor indicator of acute liver disease d/t half-life of albumin (19-21 days)
acute hepatitis etiology, risk factors, clinical manifestations
Etiology
- An inflammatory liver disease resulting in injury and necrosis
- Less than 6 month duration
- Hepatitis A-E
- CMV
- EBV
- Drug Toxicity
- ETOH abuse
Risk factors for HBV
- Illicit drug use
- Health care workers
- Male homosexuals
- Frequent blood transfusion
- Decrease immune function
- Sexual relations with HBV partners
- Newborns of mothers with HBV
Clinical manifestations
- Prodromal Period: Flulike symptoms
- Jaundice
- Anicteric hepatitis: inflammation of the liver d/t exposure from toxins and viruses
- Cholestatic hepatitis: obstruction of bile ducts at gogi apparatus
- Itching, pain upper right quadrant of abdomen, edema, coagulopathy
acute hepatic failure
*Inability of the liver to perform its normal functions
Results from:
- Hepatic failure as a primary disease
- Acute hepatic failure as a complication of chronic liver disease
- Acute hepatic failure as part of multiple organ failure
stages of hepatic encephalopathy
Stage I: Awake, apathetic, restless, sleep pattern changes, mental clouding diminished muscle coordination, mild to moderate EEG changes
Stage II: Decreased LOC, lethargy, drowsiness, asterixis, decreased reflexes, moderate to severe EEG changes
Stage III: Stupor (arousable), no spontaneous eye opening, hyperactive reflexes, seizures, rigidity, posturing- decorticate/ decerebrate severe EEG changes
Stage IV: Coma, seizures, pupil dialation, flaccidity, severe EEG changes
effects of hepatic failure on body systems
- Neurologic: Stage I-IV encephalopathy
- Cardiovascular: Pulmonary edema, hypotension
- Gastrointestinal: N/V, constipation, diarrhea, anorexia, ascites
- Hemtopioietic: Impaired coagulation, prolonged PT
- Pulmonary: Tachypnea, crackles
esophageal varices
weakness in vasculature in the esophagus and stomach that associates with a pt. who develops portal htn. Much more tender and easier to rupture
Complications of hepatic dysfunction hepatorenal syndrome
Type I HRS
Severe rapidly progressing renal failure. Very high mortality rate.
Type II HRS
Slower, chronic, progressive (associated with a pt with ascites), does not improve with the use of diuretics
Clinical Characteristics
- Prescience of liver failure
- Decreased GFRazotemia
- Oliguria/anuria
- High BUN/Creatinine ratio
Complications of hepatic dysfunction: Infection
- Kupper’s cells control inflammation and removal of gram-negative intestinal bacteria
- Loss of protein synthesis
- Both lead to increased risk of Sepsis and SIRS
collaborative management of pts with hepatic encephalopathy
- Limit protein
- Enema for constipation
- Lactulose 15-30 ml for 3-5 stools per 24 hours
- Neomycin 1-4g every 6-8 hours
- Metronidazole 250 mg 3-4 times per day
- Intubate and mechanically ventilate
collaborative managmenet of pts with hypoglycemia and acute liver disease
- 10% dextrose IV infusion
- D5 IVP as needed for rapid recovery
- POC blood glucose
collaborative management pts with metabolic abnormalities
- Monitor electrolytes and pH
- Correct abnormalities
- Administer bicarb d/t acidodic states
Collaborative managemnet of acute liver disease pts: GI hemmorrhage
- Administer Vit K
- H2 receptor antagonists
- FFP
- Platelets
collaborative managemnet: cerebral edema
- ICP monitoring
- Manitol
- Hob 20-30 degrees
- May need to be sedated with barbiturates
collaborative managment pts with hepatorenal syndrome
- Liver transplant
- Fluid resuscitation
- TIPS shunt
collaborative management of spontaneous bacterial peritonitis
- 3rd generation cephalosporin x 5-7 days
- Monitor ascitic fluid for bacterial count
collaborative managmenet of esophageal verices
Control Bleeding
- IV Vasopressin 20 U IVP followed by IV infusion 0.4-0.6 units per minute
- Somatostatin 50 mcg/hr IV
- Nitroglycerin
- FFP
Correct Bleeding
- Sengstaken-Blakemore placement
- Portal systemic shunt surgery
Prevention
- Betablockers
- Mononitrates
- Endoscopic sclerotherapy
- Endoscopic variceal banding
sentaken-blakemore placement
cause pressure to stop bleeding
normal anatomy of pancreas
- both exocrine (most of cells in pancreas, produc and release pancreatic juice to digest fat, carbs, protein) and endocrine functions (much smaller in number, clusters of islets. produce insulin (reduce amount of sugar in blood) and glucagon (increases sugar available in blood when bs is low))
- neutralize chyme
- digestive enzymes
- hormones
pancreatic acinar cells
- specialized cells which synthesize, store, and secrete digestive enzymes
- These digestive enzymes are stored in zymogen granules which serve as a compartment for inactive pro-enzymes thus preventing auto-activation.
exocrine stimulation
- The more proximal the nutrient infusion…the greater the pancreatic stimulation (dog studies)
- stomach – maximal stimulation
- duodenum – intermediate stimulation
- jejunum – minimal / negligible stimulation
- Elemental formulas tend to cause less stimulation than standard intact formulas
- intact protein > oligopeptides > free amino acids
- Intravenous nutrients (even lipids) do not appear to stimulate the pancreas
protective measures
- COMPARTMENTALIZATION - digestive enzymes are contained within zymogen granules in acinar cells
- REMOTE ACTIVATION - digestive enzymes are secreted as inactive proenzymes within the pancreas
- PROTEASE INHIBITORS – trypsin inhibitor is secreted along with the proenzymes to suppress any premature enzyme activation
- AUTO “SHUT-OFF” – trypsin destroys trypsin in high concentrations
acute pancreatitis
- Acute inflammatory process involving the pancreas
- Usually painful and self-limited
- Isolated event or a recurring illness
- Pancreatic function and morphology return to normal after (or between) attacks
etiology
- usually due to gallstones or alcohol abuse
*
acute pancreatitis associated conditions
- Cholelithiasis
- Ethanol abuse
- Idiopathic
- Medications
- Hyperlipidemia
- ERCP
- Trauma
- Pancreas divisum
- Hereditary
- Hypercalcemia
- Viral infections: Mumps, Coxsackievirus
- End-stage renal failure
- Penetrating peptic ulcer
acute pancreatitis causative drugs
- AIDS therapy: didanosine, pentamidine
- Anti-inflammatory: sulindac, salicylates
- Antimicrobials: metronidazole, sulfonamides, tetracycline, nitrofurantoin
- Diuretics: furosemide, thiazides
- IBD: sulfasalazine, mesalamine
- Immunosuppressives: azathioprine, 6-mercaptopurine
- Neuropsychiatric: valproic acid
- Other: calcium, estrogen, tamoxifen, ACE-I
hereditary pancreatitis
- Autosomal dominant with 80% phenotypic penetrance
- Recurrent acute pancreatitis, chronic pancreatitis, and 50-fold increased risk of pancreatic cancer
- Mutation in cationic trypsinogen gene (R122H)
- Other genetic defects: CFTR, SPINK1
acute pancreatitis pathogenesis
- acinar cell injury causes premature enzyme activation causing failed protective mechanisms–>autodigestion of pancreatic tissue–>local vascular issufficiency, activation of white blood cells, release of enxymes into the circulation–>local complications and distant organ failure
- failure of compartmentalization, premature activation, and overwhelming or absence of inhibitors
stages of acute pancreatitis
- STAGE 1: Pancreatic Injury
- Edema
- Inflammation
- STAGE 2: Local Effects
- Retroperitoneal edema
- Ileus
- STAGE 3: Systemic Complications
- Hypotension/shock
- Metabolic disturbances
- Sepsis/organ failure
acute pancreatitis presentation
Abdominal pain
- Epigastric
- Radiates to the back
- Worse in supine position
Nausea and vomiting
Fever
non hemorrhagic vs. hemorrhagic acute pancreatitis
non-hemorrhagic
- Short duration
- Pancreatic edema and swelling
- Little to no necrosis
- Local inflammation
- Reversible
- Good prognosis
hemorrhagic
- Long duration
- Pancreatic hemorrhage
- Extensive necrosis
- Extra-pancreatic
- Irreversible damage
- Poor prognosis- sepsis MOSF
acute pancreatitis diagnosis
Symptoms
- Abdominal pain
Laboratory
- Elevated amylase or lipase
- > 3x upper limits of normal
Radiology
- Abnormal sonogram or CT
causes of increased pancreatic enzymes
amylase _ _ lipase
Pancreatitis ↑ ↑
Parotitis ↑ Normal
Biliary stone ↑ ↑
Intestinal injury ↑ ↑
Tubo-ovarian disease ↑ Normal
Renal failure ↑ ↑
Macroamylasemia ↑ Normal
acute pancreatitis diagnosis
- EtOH: history
- Gallstones: abnormal LFTs & sonographic evidence of cholelithiasis
- Hyperlipidemia: lipemic serum, Tri>1,000
- Hypercalcemia: elevated Ca
- Trauma: history
- Medications: history, temporal association
acute pancreatitis clinical manifestations
PANCREATIC
- Mild: edema, inflammation, fat necrosis
- Severe: phlegmon, necrosis, hemorrhage, infection, abscess, fluid collections
PERIPANCREATIC
- Retroperitoneum, perirenal spaces, mesocolon, omentum, and mediastinum
- Adjacent viscera: ileus, obstruction, perforation
SYSTEMIC
- Cardiovascular: hypotension
- Pulmonary: pleural effusions, ARDS
- Renal: acute tubular necrosis
- Hematologic: disseminated intravascular coag.
- Metabolic: hypocalcemia, hyperglycemia
acute pancreatitis time course
- Cytokine release, 48 hrs, organ failure, 72 hrs
- In the early stages ofpancreatic injury and inflammation, proinflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-A, appear to be released from tissue macrophages within the pancreas.
- Neutrophil activation likely results from release of IL-8 from macrophages and endothelial cells and release of platelet-activating factor (PAF) from endothelial cells.
- Later in theprocess, release of cytokines from T-helper lymphocytes (eg, IL-2, interferon-C) may also participate in the inflammatory response [3]
predictors of severity of pancreatitis
Why are they needed?
- appropriate patient triage & therapy
- compare results of studies of the impact of therapy
When are they needed?
- optimally, within first 24 hours (damage control must begin early)
severity scoring system pancreatiis
Ranson and Glasgow Criteria (1974)
- based on clinical & laboratory parameters
- scored in first 24-48 hours of admission
- poor positive predictors (better negative predictors)
Computed Tomography Severity Index
- much better diagnostic and predictive tool
- optimally useful at 48-96 hours after symptom onset
ranson criteria alcohol pancreatiis
At admission
- Age > 55 years
- WBC > 16,000
- Glucose > 200
- LDH > 350 IU/L
- AST > 250 IU/L
Within 48 hours
- HCT drop > 10
- BUN > 5
- Arterial PO2 < 60 mm Hg
- Base deficit > 4 mEq/L
- Serum Ca < 8
- Fluid sequestration > 6L
higher point values=higher mortality rates
less than 2=1% mortality rate
3-4= 16%
5-6=40%
7-8=100%
glasgow criteria non-alcoholic pancreatitis
Glasgow prognostic score: (NOTE PANCREAS ACRONYM)
- PaO2 < 8kPa (60mmhg)
- Age > 55 years
- Neutrophils: (WBC >15 x109/l
- Calcium < 2mmol/l
- Renal function: (Urea > 16mmol/l)
- Enzymes: (AST/ALT > 200 iu/L or LDH > 600 iu/L)
- Albumin < 32g/l
- Sugar: (Glucose >10mmol/L)
score > 8 points predicts 11% to 18% mortality
acute physiology and chronic health evaluation (apache II)
- score > 8 points predicts 11% to 18% mortality
- Online calculator
- Hemorrhagic peritoneal fluid
- Obesity
- Indicators of organ failure
- Hypotension (SBP <90 mmHG)
- tachycardia > 130 beat/min
- PO2 <60 mmHg
- Oliguria (<50 mL/h)
- Increasing BUN and creatinine
- Serum calcium < 1.90 mmol/L (<8.0 mg/dL)
- serum albumin <33 g/L (<3.2.g/dL)
CT severity Index
looking at the results of looking at the pancreas itself, giving a grade and a score. Best way to judge severity
appearance:
- normal: grade A, score 0
- enlarged:grade B, score 1
- inflamed: grade c, score 3
- 1 fluid collection: D, score 4
- 2 or more collections: E, score 5
Necrosis:
- None: score 0
- <33%: score 2
- 33-50%: score 4
- >50%: score 6
Score 1-2: 4% morbidity, 0% mortality
Score 7-10: 92% morbidity, 17% mortality
severe acute pancreatitis
Scoring systems
- >/=3 Ranson criteria
- >/=8 APACHE II points
- >/= 5 CT points
Organ failure
- shock (SBP < 90 mmHg)
- pulmonary edema / ARDS (PaO2 < 60 mmHg)
- renal failure (Cr > 2.0 mg/dl)
Local complications
- fluid collections –>pseudocysts
- necrosis (mortality 15% if sterile, 30-35% if infected)
- abscess
assessment findings with pancreatitis
- Anorexia
- Abdominal rigidity/ tenderness
- N/V
- Pain – sudden, knifelike
- Diminished/ absent Bowel sounds
- Diminished breath sounds
- Cullen’s sign: bruising around the umbilicus
- Grey turner’s sign: flank bruising
- Altered LOC
- Chvostek’s sign: tapping in front of ear, mouth twitches
- Trousseau’s sign: latent tetany is a medical sign observed in patients with low calcium
- Non-cardiogenic pulmonary edema heard most often on Left side
treatment of mild pancreatitis
- Pancreatic rest
- Supportive care
- fluid resuscitation – watch BP and urine output
- pain control
- NG tubes and H2 blockers or PPIs are usually not helpful
- Refeeding (usually 3 to 7 days)
- bowel sounds present
- patient is hungry
- nearly pain-free (off IV narcotics)
- amylase & lipase not very useful here
*mild panc – support is all that’s needed
*hypotension probably predisposes to necrosis (poor microcirculation)
treatment of severe pancreatitis
- Pancreatic rest & supportive care
- fluid resuscitation* – may require 5-10 liters/day
- careful pulmonary & renal monitoring – ICU
- maintain hematocrit of 26-30%
- pain control – PCA pump Why Not Morphine?
- correct electrolyte derangements (K+, Ca++, Mg++)
- Rule-out necrosis
- contrasted CT scan at 48-72 hours
- prophylactic antibiotics if present
- surgical debridement if infected
- Nutritional support
- may be NPO for weeks
- TPN vs. enteral support (TEN)
Role of ERCP
Gallstone pancreatitis
- Cholangitis
- Obstructive jaundice
Recurrent acute pancreatitis
- Structural abnormalities
- Neoplasm
- Bile sampling for microlithiasis
Sphincterotomy in patients not suitable for cholecystectomy
* Sedated, scope ran down through mouth to see what’s going on
nutrition in acute pancreatitis
Metabolic stress
- catabolism & hypermetabolism seen in 2/3 of patients
- similar to septic state (volume depletion may be a major early factor in the above derangements)
Altered substrate metabolism
- increased cortisol & catecholamines
- increased glucagon to insulin ratio
- insulin resistance
Micronutrient alterations
- calcium, magnesium, potassium, etc
systemic changes in acute pancreatitis
Hyperdynamic
- Increased cardiac output
- Decreased systemic vascular resistance
- Increased oxygen consumption
Hypermetabolism
- Increased resting energy expenditure
Catabolism
- Increased proteolysis (breakdown) of skeletal muscle
reduce oral intake in acute pancreatitis
- Abdominal pain with food aversion
- Nausea and vomiting
- Gastric atony ( decresed motility)
- Ileus
- Partial duodenal obstruction
Factors differentiating mild vs. severe pancreatitis
mild
- Admission 80%
- Pancreatitc Necrosis: No
- Oral diet within 5 days: 80%
- Morbidity: 8%
- Mortality: 3%
Severe
Admission 20%
Pancreatitc Necrosis: Yes
Oral diet within 5 days: 0%
Morbidity: 38%
Mortality: 27%
TPN in acute pancreatitis
- delay until volume repleted & electrolytes corrected
- check triglycerides first – goal <400
- lipids are OK to use (possible exception of sepsis)
- monitor glucose levels carefully
- can see insulin insufficiency and resistance
- may need to limit calories at first
- separate insulin drip may be needed
Benefit or harm?
- early uncontrolled studies suggested benefit
- two retrospective studies (70’s & 80’s) showed no benefit with TPN in pancreatitis
- 1987 – randomized study of early TPN vs. IVF alone showed more sepsis, longer stays, & no fewer complications with TPN
When to use TPN?
- jejunal access is unavailable
- ileus prevents enteral feeding
- patients in whom TEN clearly exacerbates pancreatitis
total enteral nutrition in severe pancreatitis
- may start as early as possible
- when emesis has resolved
- ileus is not present
- nasojejunal route preferred over nasoduodenal
- likely decreases risk of infectious complications by reducing transmigration of colonic bacteria
