Portal HTN/Chronic Liver Failure/Last Nichols Flashcards
1
Q
Liver Blood Flow
A
- 30% Hepatic Artery
- 70% Portal Vein (Splenic & Splanchnic)
2
Q
Pressure=
A
flow x resistance
- cirrhosis
- fibrosis w/distortion of vasculature
- sinusoids to capillaries
- inc. blood flow to stomach & intestines
3
Q
Portal HTN
A
- venous collaterals form from distal esophagus to rectum
- anterior collaterals via umbilical vein
- posterior collaterals via retroperitoneal vains, splenorenal shunts
4
Q
Varices
A
- tortuous venous collaterals under high pressure (high pressure bleeding)
- 50% of newly diagnosed cirrhotics
- inc. up to 8%/year
- 32% bleed within 2 years
- major cause of death
- thrombocytopenia
- coagulopathy (synthetic impairment of clotting factors)
5
Q
Treatment of Portal Vein HTN
A
- volume resuscitation
- correction of coagulopathy
- splanchnic vasoconstriction
- dec. blood flow to stomach and intestines
- dec. blood flow via collaterals
- Vasopression
- Somatostatin (block vasodilators)
6
Q
Natural History of Variceal Hemorrhage
A
- mortality 42% in 6 weeks
- 60% of early deaths due to bleeding
- approximately 1/3 of patients had rebleeding within 6 weeks
- 1 year survival 34%
7
Q
Treatment of Variceal Hemorrhage
A
- endoscopic therapy to sclerose or band the varices
- decrease portal pressure (beta blockers, transjugular intrahepatic portosystemic shunt, liver transplantation, surgical portosystemic shunt)
8
Q
Child Pugh Classification
A
- albumin
- prothrombin time
- bilirubin
- ascites
- encephalopathy
- Child A, B, C
9
Q
Ascites
A
- inc. resistance to portal venous flow
- inc. flow to portal vein
- inc. lymphatic flow
- leakage of lymphatic flow from liver and intestines
- inc. Portosystemic shunting of vasodilators
- Systemic vasodilation
- dec. renal perfusion
- inc. renal vasoconstriction
- inc. Renin-Angiotension activity
- Inc. Sodium reabsorption
10
Q
Ascites Causes?
A
- decreased renal clearance
- severe liver disease is associated with sodium retention & decreased creatinine clearance
- Hep C can also cause renal disease
11
Q
Why is Ascites important?
A
- tense ascites, pressure on diaphragms & stomach, difficulty breathing and eating
- hepatic hydrothorax
- spontaneous bacterial peritonitis
12
Q
Spontaneous Bacterial Peritonitis
A
- large amount of undrained fluid
- low protein ascites
- low complement
- bacterial translocation from intestines to blood
- transient bacteremia infects the ascites
13
Q
Treatment of Ascites
A
- sodium restriction
- diuretics
- treat the liver disease
- large volume paracentesis
- correct the portal HTN
- transugular portosystemic shunt
- surgical portosystemic shunt
- liver transplantation
14
Q
Portal HTN causes?
A
life threatening complications
15
Q
Chronic Liver Failure (TYPES)
A
- hepatic encephalopathy
- hepatorenal syndrome
- IgA nephropathy
- other renal complications with liver disease
16
Q
Hepatic Encephalopathy
A
-acute liver failure
-portosystemic shunt without liver failure
-chronic liver failure:
precipitated
spontaneous
recurrent
17
Q
Mechanisms of Hepatic Encephalopathy
A
- ammonia, nitrogenous wastes
- inc. intracellular gluatamine
- astrocyte swelling, Cerebral edema
- Inflammatory cytokines alter blood-brain barrier
- Inc. Benzodiazepine receptors
- inc. Neurosteroids, inc. GABA receptor activity
- Manganese - neurotoxin which deposits in basal ganglia
18
Q
Acute Hepatic Encephalopathy
A
- acute liver failure: coagulopathy and altered mental status within 2 weeks of jaundice
- alteration of BBB
- associated with acute cerebral edema
- cerebral edema results in cerebral herniation
- major cause of death from acute liver injury
19
Q
Chronic Hepatic Encephalopathy
A
- slow & subtle onset
- often noticed by family members
- milder symptoms frequently missed by coworkers or physicians
20
Q
Stages of hepatic encephalopathy
A
- Grade I: irritability, insomnia, agitation
- Grade II: indifferent, personality change, short term memory impairment, mildly disoriented about time or place
- Grade III: drowsy but arousable, significantly confused & disorented to time & place
- Grade IV: coma
21
Q
Physical Exam for Hepatic Encephalopathy
A
- neuro exam
- alert, orientation to time, place, date, President’s name, family members Bday, maiden names
- Asterixis: hyperextend wrists and observe for repetitive movement “flap”, inability to perform sustained grip of hand
- myoclonus: with hyperrextension of ankles
- absence of sensory, motor or cerebellar deficit to suggest another etiology for altered mentation
- absence of autonomic hyperactivity, tachycarida, HTN
- absence of sensory, motor or cerebellar deficit to suggest another etiology for altered mentation
22
Q
Chronic Hepatic Encephalopathy Outcome
A
- generally reversible with treatment
- with long standing chronic hepatic encephalopathy: permanent brain damage can occur
- mild decrease in mentation, calculation
- rarely results in irreversible dementia
- rarely permanent movement disorders
23
Q
Treatment for Hepatic Encephalopathy
A
Treat the precipitating conditions:
- Hypovolemia: correct causes-diuretics, medications which caused excessive diarrhea
- Hypokalemia
- GI bleeding
- Prescribed medications, sedatives, substance abuse
- Infection: evaluate for common systemic infections, meningitis
- Exclude intracranial hemorrhage, falls with thrombocytopenia, coagulopathy (inc. INR)
24
Q
Treatment for Hepatic Encephalopathy: Lactulose
A
- poorly absorbable sugar
- cathartic
- decreased intestinal pH
- decreases glutamine absorption
- reduces synthesis & absorption of NH3
25
Treatment for Hepatic Encephalopathy: Zinc Sulfate
- zinc is cofactor in NH3 metabolism, zinc deficiency is common in liver disease
- correction of zinc deficiency is part of the treatment of encephalopathy
26
Treatment for Hepatic Encephalopathy: antibiotics
- alter intestinal flora
- decreased NH3
- decrease intestinal mucosal glutaminase
- decrease coliform bacterial which produce urease and convert urea to NH3
27
Mechanisms of Treatment for Hepatic Encephalopathy
- nutrition improves the underlying liver disease
- skeletal muscle metabolizes NH3
- malnutrition is common in liver patients
- protein restriction is not helpful
- high vegetable proteins with increased branched chain amino acids advised
28
Nutrition & Hepatic Encephalopathy
- protein restriction was not recommended in 1963
| - it should not be part of orders today
29
Renal Complications associated with Liver Disease
- hepatorenal syndrome
- IgA nephropathy
- membranoproliferative glomerulonephritis
- membranous glomerulonephritis
30
Hepatorenal Syndrome
- most feared complications of acute liver failure or cirrhosis
- liver failure cause renal arterial vasoconstriction and renal failure
- not associated with underlying renal parenchymal abnormality
- generally reversed with correction of liver failure such as with transplantation
31
Hepatorenal Syndrome: What Happens?
- cirrhosis & ascites
- serum creatinine >1.5mg/dL
- no imporvement (decrease 500mg protein per day)
32
Diagnosis of Hepatorenal Syndrome
- exclusion
| - lack of return of renal function with intravascular volume repletion
33
Hepatorenal Syndrome Type I
- rapid, worsening
| - creatinine >2.5mg/dL or decrease CrC <20ml/min in 2 weeks
34
Mechanism of Hepatorenal Syndrome
- peripheral artery vasodilaton
- stimulation of renal sympathetic nervous system, renin-angiotension-aldosterone system
- cardiac dysfunction, impaired contractility
- cardiac dysfunction (impaired contractility)
- cytokines & vasoactive mediators
35
Hepatorenal Syndrome Type II
-slow progression, often with worsening liver disease
36
Treatment for Hepatorenal Syndrome
- IV volume repletion
- treat infection
- avoid meds that worsen renal function (NSAIDS)
- avoid contrast (renal injury)
- optimize renal perfusion w/Midodrine & Octreotide
* **Liver transplant***
* **Hemodialysis until liver transplant***
37
IgA Nephropathy
- liver disease most common cause of secondary
- inc. deposition of IgA, C3, and other immunoglobuliins in 35-90% of cirrhosis patients
- dec. hepatic clearance of IgA with cirrhosis and portal hypertension (with collateral blood flow around liver)
38
Membranoproliferative Glomerulonephritis
- associated with chronic Hep. C
- cryoglobulinemia- abnormal protein in the blood which precipitates with cold temperatures
- initially associated with Hep. C
- attributed to immune complex formation with chronic Hep. C
39
Inborn Errors of Metabolism
- involve liver
- babies: often 24-72 hrs: poor feeding, lethargy, vomiting, seizures, shock
- later presentations: often >28 days, failure to thrive, developmental delay, vomiting, respiratory or pyschomotor
40
Tryosinemia Urine Odor
boiled cabbage
| rotten eggs
41
Phenylketonuria Urine Odor
mousy or musty
42
Trimethylaminuria Urine Odor
rotting fish
43
Isovalaric acidemia Urine Odor
sweaty feet
44
Maple Syrup urine disease Urine Odor
Maple Syrup
45
Do you have to smell patients urine?
no, sometimes emanated from breath or sweat
| -majority of patients with odor do not have inborn errors of metabolism
46
History for Inborn Errors of Metabolism
- family history (autosomal recessive)
- Dietary history (specific sugary, proteins, can cause manifestations)
- Poor feeding + lethargy + seizures suggests hypoglycemia or hypocalcemia
- older children may present with episodic acute manifestations of disease
47
Tests for Inborn Errors of Metabolism
ammonia, bicarb, pH, glucose, electrolytes, bilirubin, lactate, CBC, urine dipstick, urine "clinitest" for reducing substances
- if ammonia, bicarb, pH normal = aminoacidopathy
- episodic: lab tests normal between
- freeze liver biopsy for enzyme assays
48
Tryosinemia Type I
- aminoacidopathy due to fumaryl-aceto-acetase deficiency
- prevalent in French Canadians
- Autosomal recessive
- backup of metabolism of tyrosine leads to buildup of metabolites that are toxic to liver & kidney (mutagenic in liver)
- liver toxicity manifested by steatosis, cholestasis, nodular regeneration with cholangiolar proliferation, cirrhosis,dysplasia and (37%) hepatocellular carcinoma
49
Tyrosinemia Type I: gross pathology
- cirrhosis with very large regenerative nodules
| - yellow-orange due to steatosis & cholestasis
50
Tyrosinemia Type I: microscopic pathology
- steatosis & cholestasis (dark bile plugs "black")
| - dysplasia
51
Tyrosinemia Type I: Classic Presentation
-first few months of life, failure to thrive, vomiting, diarrhea (bloody), jaundice, lethargy, coma, death (fulminant hepatic failure)
52
Tyrosinemia Type I: Diagnosis
- high urine succinylacetone
| - DNA test for specific mutation (100% french canadians, 28% worldwide)
53
membranous glomerulonehritis
associated with C & D
54
Tyrosinemia Type I: Treatment
- low-tyrosine diet, herbicide called NTBC (inhibits upstream enzyme that causes tyrosinemia type II)
- liver thansplantation
55
Tyrosinemia Type I: Prognosis
much better if treated early
56
Ornithine Transcarbamylase (OTC) Deficiency
- most common urea cycle disorder
- X-linked
- patients normal at birth until fed protein, then develop irritability, poor feeding, vomiting, lethargy, respiratory distress, hypotonia, seizures, coma and respiratory arrest due to hyperammonemia
57
Ornithine Transcarbamylase (OTC) Deficiency: Diagnosis
blood & urine amino acid levels
liver enzyme assay
DNA test
58
Ornithine Transcarbamylase (OTC) Deficiency: Treatment
emergency: IV benzoate, phenylacetate & citrulline
| long term: protein restriction, liver transplant
59
Gaucher's Disease
- beta-glucocerebrosidase deficiency
- adult form = the most common lysosomal storage disease
- autosomal recessive (Jews)
60
Gaucher's Disease: Microscopic
-Kupffer cells and macrophages with expanded crinkled cytoplasm
61
Signs of Gaucher's Disease
- splenomegaly=most common initial sign
| - pancytopenia, bone pain
62
Gaucher's Disease: Diagnosis
-assay of beta-glucosidase in white blood cells
63
Gaucher's Disease: Treatment
enzyme replacement where available ($)
64
Glycogen Storage Disease Type I (Von Gierke)
deficiency of glucose-6-phosphatase (catalyzing conversion of glucose-6-phosphate to glucose), resulting in decreased hepatic glucose production and accumulation of glycogen in liver, kidney and intestine
65
Glycogen Storage Disease Type I (Von Gierke): Classical Presentation
- in first year of life: marked hepatomegaly & hypoglycemia
| - lactic acidosis, hyperlipidemia, hyperuricemia
66
Glycogen Storage Disease Type I (Von Gierke): Diagnosis
DNA test
67
Glycogen Storage Disease Type I (Von Gierke): Microscopic pathology
- cytoplasmic glycogen accumulation
| - hepatomas
68
Porphyrias
- diverse group of inborn errors of metabolism involving enzymes in heme synthesis (not all in bone marrow, 20% liver)
1. acute
2. cutaneous
69
Porphyrias: Clinical Presentation
- porphyria cutanea tarda (heal by scaring)
- onset after 20 years old
- skin vesicles and bullae with sun exposure, attributed to formation of reaction oxygen species from porphyrin compounds, especially uroporphyrinogen
70
Acute Intermittent Porphyria
- autosomal dominant
- porphobilinogen-deaminase (PBGD) deficiency
- body's ability to effectively supply heme is altered, alteration can create shortages in times of need
- abnormal accumulation/build-up of bio-chemicals in body
- 5x more female
71
Acute Intermittent Porphyria: Symptoms precipitated by?
-drugs, alcohol, smoking, steroids, oral contraceptives
72
Acute Intermittent Porphyria: Symptoms
- abdominal pain
- vomiting
- tachycardia
- constipation
- neck, back, head pain
- paresis
- mental
73
Acute Intermittent Porphyria: Urine
-dark, even purple with standing
74
Acute Intermittent Porphyria: Diagnosis
urine test for porphobilinogen (PBG)
75
Acute Intermittent Porphyria: Treatment
IV heme
76
Acute Intermittent Porphyria: Prevention
-avoiding precipitants
77
Pyloric Stenosis
```
uncommon (0.35% births), 5x males
-genetic predisposition & environmental triggers
200x if monozygotic twin
4.62x more with bottle-feeding
erythromycin associated
```
78
Pyloric Stenosis: Pathology
hypertrophy of pyloric muscle
79
Pyloric Stenosis: Presentation
3-6 week old baby
- immediate postprandial, non-bilioius, projectile vomiting & demands to be re-fed soon after
- emaciated & dehydrated with "olive-like" mass at lateral edge of rectus abdominus muscle in right upper quadrant of abdomen (92%)
- peristaltic waves seen from left to right just before emesis
80
Pyloric Stenosis: Diagnosis
H&P +/- radiology
81
Pyloric Stenosis: Treatment
surgery (pyloromyotomy)
