CNS and Liver in Pregnancy
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  • Folic acid supplementation — Low serum folate levels in women with epilepsy are independently associated with an increased risk of major fetal malformations [3] . It has not yet been conclusively determined if folic acid supplementation prevents neural tube defects in women receiving AEDs. However, animal studies have shown that valproate and phenytoin decrease the concentration of certain forms of folate and are associated with neural tube defects [4,5] .
  • Pregnancy is accompanied by many alterations in drug metabolism, including increased liver metabolism, renal clearance, and volume of distribution, and decreased gastrointestinal absorption and plasma protein binding [15,23,24] . As an example, for AEDs that are highly protein bound (eg, phenytoin, valproate), the total plasma drug level may decrease with impaired protein binding, but the physiologically important free or unbound drug concentration may not change. As a result, free drug levels for these AEDs may be more reliable during pregnancy. However, medication dosage should be adjusted if the patient's seizures are not controlled, not because the free or total level has decreased.
  • immunisation
  • The origin of the liver disease associated with hyperemesis gravidarum is unclear. Not all affected patients have liver disease; therefore, the vomiting does not appear to be secondary to the liver involvement. Starvation alone does not seem to be an adequate explanation for the liver dysfunction, particularly in as much as biopsy in affected patients fails to show the fatty infiltration typical of starvation .
  • pedaitrician
  • Low haptoglobin – most sensitive measure for hemolysis. Seen before plt count drops.
  • Maternal complication seen in 12-65% of cases
  • 50% mortality due to hepatic hematoma with rupture

CNS and Liver in Pregnancy Presentation Transcript

  • 1. CME ON MEDICAL DISORDERS IN PREGNANCY NERVOUS SYSTEM AND LIVER Prof. Dr. S Sundar’s Unit Dr. Deepu Sebin, PG in Internal Medicine
  • 2. CNS in Pregnancy Liver Challenges us with the diagnosis Challenges are both in diagnosis and treatment Brain and Liver – There are changes with pregnancy , but not much ! Liver in Pregnancy CVAs and Seizures Pregnancy specific liver diseases
  • 3. CVA during pregnancy
    • Pregnancy and the postpartum period are associated with a marked increase in the relative risk and a small increase in the absolute risk of ischemic stroke and intracerebral hemorrhage, with the highest risk during the puerperium.
  • 4.
    • Most cerebral infarctions associated with pregnancy are due to arterial occlusion , not cerebral venous thrombosis 1
    • Ischemic and hemorrhagic strokes have been reported in roughly equal proportions.
            • 1.Jaigobin and Silver ( Stroke , 2000), McGriger etal 2003, NEFh study 1999
  • 5. Stroke and Pregnancy: Subarachnoid Hemorrhage
    • Subarachnoid hemorrhage (SAH) is a leading cause of non-obstetric-related maternal death Which is often not identified.
    • Incidence of SAH from aneurismal rupture in pregnancy ranges from 3 to 11 per 100,000 pregnancies 2
    • 50% of all aneurismal ruptures in women below the age of 40 years are pregnancy related 3
    1. Visscher HC, Visscher RD. Indirect obstetric deaths in the state of Michigan 1960–1968. Am J Obstet Gynecol 1971;109:1187–96. 2. Sharshar T, Lamy C, Mas JL. Incidence and causes of strokes associated with pregnancy and puerperium: a study in public hospitals of Ile de France. Stroke 1995;26:930–6. 3. Barrett JM, Van Hooydonk JE, Boehm FH. Pregnancy-related rupture of arterial aneurysms. Obstet Gynecol Surv 1982;37:557–66.
  • 6. Risk Factors
    • Age >35 years
    • Black Ethnicity
    • HTN: Pre-eclampsia and Eclampsia
    • Hypercoagulable state of pregnancy
    • Heart Disease
    • Smoking
    • Diabetes
    • Lupus
    • Sickle Cell Disease
    • Migraine Headache
    • Alcohol and Substance Abuse
    • Caesarean Delivery
    • Fluid and Electrolyte Disorders
    • Thrombophilia
    • Multiple Gestation
    • Greater Parity
    • Postpartum Infection
    • AntiPhospholipid Antibody Syndrome
    • Gestational Trophoblastic Disorder
    • Peripartum cerebral angiopathy
  • 7. Risk Factors Risk Factors
    • Age >35 years
    • Black Ethnicity
    • HTN: Pre-eclampsia and Eclampsia
    • Hypercoagulable state of pregnancy
    • Heart Disease
    • Smoking
    • Diabetes
    • Lupus
    • Sickle Cell Disease
    • Migraine Headache
    • Alcohol and Substance Abuse
    • Caesarean Delivery
    • Fluid and Electrolyte Disorders
    • Thrombophilia
    • Multiple Gestation
    • Greater Parity
    • Postpartum Infection
    • AntiPhospholipid Antibody Syndrome
    • Gestational Trophoblastic Disorder
    • Peripatrum Cerebral Angiopathy
  • 8. Stroke and Pregnancy: Pre-eclampsia and Eclampsia
    • The proportion of patients with pregnancy-related stroke who have pre-eclampsia or eclampsia is 25-45% 1
    • Proposed mechanisms for increased risk of stroke in pre-eclampsia and eclampsia: 2
      • Endovascular dysfunction
      • Abnormal cerebral autoregulation resulting in higher cerebral perfusion pressures, which may result in barotrauma and vessel damage
      • Hemoconcentration due to third spacing of intravascular fluids
      • Activation of the coagulation cascade with micro-thrombi formation
    • Cerebral hemorrhage is the most common cause of death in women with eclampsia 3
    • Stroke is the most common cause of death in women with HELLP syndrome 4
    • Women with a history of pre-eclampsia are 60% more likely to have a non-pregnancy-related ischemic stroke 5
    1. Sharshar T, Lamy C, Mas JL. Incidence and causes of strokes associated with pregnancy and puerperium: a study in public hospitals of Ile de France. Stroke 1995;26:930–6. 2. Treadwell SD, Thanvi B, Robinson TG. Stroke in pregnancy and the puerperium. Postgrad Med J of BMJ 2008;84:238-45. 3. Okanloma KA, Moodley J. Neurological complications associated with the preeclampsia/eclampsia syndrome. Int J Gynaecol Obstet 2000;71:223–5. 4. Isler CM, Rinehart BK, Terrone DA, et al. Maternal mortality associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1999;181:924–8. 5. Brown DW, Dueker N, Jamieson DJ, et al. Preeclampsia and the risk of ischemic stroke among young women. Stroke 2006;37:1055–9 .
  • 9. 1. Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ 2009;338:b664.
  • 10. Stroke and Pregnancy: Migraine
    • Migraine was thought to be associated with a with a 17 -fold increased risk of pregnancy-related stroke 1
    • Large Inpatient Sample (2000-2003): 2
      • Strongest association between migraine and ischemic stroke (OR=30.7)
      • Intracranial hemorrhage strongly associated with migraine (OR=9.1)
      • Pre-eclampsia and venous thromboembolism/PE associated with migraine
      • CVT and SAH were not associated with migraine
    1. James AH, Bushnell CD, Jamison MG, Myers ER. Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol 2005;106:509-16. 2. Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ 2009;338:b664.
  • 11. Stroke and Pregnancy: Migraine
    • Overlapping pathophysiological mechanisms exists.
    • Migrainers have increased peripheral and central blood pressure, a decreased diameter and compliance of superficial muscular arteries , and decreased endothelial dilatation response to hyperemia compared to controls 1.
    • Active migraine during pregnancy can be viewed as a marker of vascular diseases, especially ischemic stroke 2.
    1. Vanmolkot F, Van Bortel L, de Hoon J. Altered arterial function in migraine of recent onset. Neurology 2007;68:1563-70. 2. Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ 2009;338:b664.
  • 12.
      • Increased von Willebrand factor,Factor 8, fibrinogen
      • Reduced protein S concentrations
      • Increased plasminogen activator inhibitors 1 and 2
      • Platelet aggregation
    Barotrauma during deliver due to raised ICP due to straining Gravid uterus compressing the vessels
  • 13. Stroke and Pregnancy: Cerebral Vein Thrombosis (CVT)
    • Occlusion of the dural venous sinuses or cortical veins can result in venous infarction and hemorrhage with associated focal neurological signs and symptoms
      • Impaired absorption of CSF
      • Intracranial HTN
      • Headache, vomiting, papilledema
      • Seizures, coma, death
    • Risk of CVT is increased in the puerperium due to pregnancy-related hypercoagulability
    • Incidence rate of 11.6 cases of peripartum CVT per 100,000 deliveries 1
    1. Lanska DJ, Kryscio RJ. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis. Stroke 2000;31:1274–82.
  • 14. Stroke and Pregnancy: Cerebral Vein Thrombosis (CVT)
    • Treatment is complicated by uncertainty regarding the safety of antithrombotic agents during pregnancy
    • Low dose aspirin appears to be safe for the fetus after the first trimester
    • Warfarin may be safe for the fetus after the first 12 weeks, but is not usually recommended during pregnancy because of teratogenic risk
    • American Heart Association/American Stroke Association recommendations for high-risk thromboembolic complications in pregnancy:
      • Adjusted-dose unfractionated (UFH) heparin throughout pregnancy with PTT monitoring
      • Adjusted-dose low-molecular-weight heparin (LMWH) throughout pregnancy with factor Xa monitoring
      • UFH or LMWH until week 13 followed by warfarin until the middle of the third trimester, when UFH or LMWH is reinstituted until delivery 1
    1. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. Stroke 2006;37:577–617.
  • 15. Stroke and Pregnancy: Postpartum Cerebral Angiopathy
    • Postpartum cerebral angiopathy (PCA) is a cerebral vasoconstriction syndrome
    • Also known as eclamptic vasospasm or Call-Fleming syndrome
    • Exact pathophysiology unknown
    • Symptoms usually occur in late pregnancy or early puerperium, and may be associated with pre-eclampsia or eclampsia 1,2
      • Recurrent thunderclap headache
      • Focal neurological deficits (transient or permanent)
      • Photosensitvity
      • Vomiting
      • Altered level of consciousness
      • Seizures
    1. Treadwell SD, Thanvi B, Robinson TG. Stroke in pregnancy and the puerperium. Postgrad Med J of BMJ 2008;84:238-245. 2. Singhal AB, Kimberly WT, Schaefer PW, Hedley-Whyte ET. Case 8-2009: A 36-year-old woman with headache, hypertension and seizure 2 weeks post partum N Engl J Med 2009;360:1126-37.
  • 16. Stroke and Pregnancy: Postpartum Cerebral Angiopathy
    • Radiological features
      • Multifocal segmental narrowing of the cerebral arteries
      • Reversibility and resolution of narrowing within 3 months
      • Vasogenic edema
      • Border-zone ischemic strokes
    • Cerebrospinal Fluid
      • Usually normal (Differentiates PCA from SAH)
    • Pathology
      • May be necessary to distinguish PCA from vasculitis
      • Early hypertensive vascular changes and subendothelial thickening have been described 1
      • No pathological changes specific to PCA have been described
    • Treatment
      • Calcium channel blockers (IV, PO or intra-arterial)
      • Corticosteroids
    1. Singhal AB, Kimberly WT, Schaefer PW, Hedley-Whyte ET. Case 8-2009: A 36-year-old woman with headache, hypertension and seizure 2 weeks post partum N Engl J Med 2009;360:1126-37.
  • 17. Stroke and Pregnancy: Postpartum Cerebral Angiopathy 1. Singhal AB, Kimberly WT, Schaefer PW, Hedley-Whyte ET. Case 8-2009: A 36-year-old woman with headache, hypertension and seizure 2 weeks post partum N Engl J Med 2009;360:1126-37.
  • 18. STROKE AND PREGNANCY Diagnostic Imaging
  • 19. Natural background exposure in a costal area is ~300 mrad per year.
    • Maximum estimated fetal absorbed dose of ionizing radiation is
      • 50 mrad for a head CT
  • 20. Stroke and Pregnancy: Ionizing Radiation
    • Estimated increase in lifetime risk of developing cancer after fetal exposure form a head CT is 0.07% 4
    • Analysis suggests that pregnant women exposed to less than 5000 mrad have no additional risk to the fetus 4
    • There is no direct evidence that fetal exposure to ionizing radiation used in diagnostic imaging causes cancer or birth defects
    • MRI does not involve ionizing radiation
      • Any long-term effects are yet to be determined
    1. Hart D, Hillier MC, Wall BF, et al. Doses to patients from medical x-ray examinations in the UK – 1995 review. Chilton: NRPB-R289, 1996. 2. Osei EK, Faulkner K. Fetal doses from radiological examinations. Br J Radiol 1999;72:773–80. 3. NRPB. Diagnostic medical exposures: exposure to ionizing radiation of pregnant women. Doc NRPB 1993;4:5–14. 4. Treadwell SD, Thanvi B, Robinson TG. Stroke in pregnancy and the puerperium. Postgrad Med J of BMJ 2008;84:238-245.
  • 21. Seizure Disorder and Pregnancy
  • 22. How Bad are AEDs ?
    • All Anti Epileptic drugs have teratogenic effects
    • Lack of conclusive data on the comparative teratogenicity of different AEDs.
    • A possible exception is valproate. Early results from pregnancy registries and most recent cohort studies suggest a trend toward higher teratogenicity with valproate than with other AEDs
  • 23.
    • Seizures cause fetal bradycadia and fetal hypoxia
    • Seizure cause considerable increase in maternal mortality
    • Anti epileptic drugs
    • All can have harmful effects for fetus
  • 24. 1.Know epileptic patient, planning for a pregnancy
  • 25. Does She even Need AED ? Polytherapy to Monotherapy Therapy Taper to Lowest Possible Dose Replace Valproate Add Folate 4 mg, Vitamin K in third trimester Adequate Sleep Plan conception after 6 months Use barrier contraception
  • 26. 2.A pregnant epileptic patient
  • 27. Does She even Need AED ? Polytherapy to Monotherapy Therapy Taper to Lowest Possible Dose, Replace Valproate Add Folate 4 mg. Vitamin K in 3 rd trimester Adquate Sleep Plan conception after 6 months Use barrier contraception Beware of Possble dilution Consider plams drug level monitoring if possible
  • 28. 3.A patient with a seizure in pregnancy or delivery or postpartum Emergency
  • 29. Consider Masulf IF: >20 wks of pregnancy or postpartum Seizure not controlled with IV AED & Sedation Any Features of Preeclampsia in current or previous pregnancy ? No Yes * The initial diagnosis of preeclampsia may be postpartum Suspect CVA/CVT/CNS infection Manage as similar to non pregnant seizure Magnesium Sulphate Diazepam Lorazepam if not resolving
  • 30. Magnesium Sulphate
    • A observations drug in the past, Now a evidence based drug.
    • Magnesium's mechanism of action as an anticonvulsant in preeclampsia/eclampsia is not clearly understood.
    • Some possibilities include
      • vasodilatation of the cerebral vasculature,
      • inhibition of platelet aggregation,
      • protection of endothelial cells from damage by free radicals,
      • prevention of calcium ion entry into ischemic cells,
      • decreasing the release of acetylcholine at motor end plates within the neuromuscular junction
      • as a competitive antagonist to the glutamate N-methyl-D-aspartate receptor (which is epileptogenic)
    Magnesium Sulpahte is an Anti Eplileptic Drug,which is has its maximum effect when the seizures are due to Eclampsia
  • 31.
    • A tonic-clonic seizure occurs during labor in 1 to 2% of women with epilepsy, and another 1 to 2% 24hrs after delivery. It is therefore essential to maintain a plasma AED level known to protect against seizures during the third trimester and during delivery and postpartum.
    • Doses must not be missed during the period of labor.
  • 32. Liver
  • 33. Liver in a Normal Pregnancy
    • In Normal Pregnancy
    • Physical – Palmar Erythema, Spider Naevi
      • Pathologically essential normal except for increased Endoplasmic Reticulum.
      • Liver Flow is same ( Excess blood because of the increased Cardiac Output is shunted out to the placenta)
  • 34. Normal Pregnancy Viral Hepatitis H. Gravidarum IHCP HEELP AFLP S .Bilurubin Slightly down AST Normal ALT Normal ALP 3x in 3 rd timester GGT Normal S. Bile Acid Normal PT, INR Normal S.Ammonia Normal Total Count Normal Platelets Normal RBS Normal S.Creatine Normal LDH Normal DIC No
  • 35.
    • Preexisting Liver Diseases
    • Liver diseases coincidental with but not induced by pregnancy
    • Liver Disease Induced by Pregnancy
  • 36. Preexistent liver diseases
      • Portal hypertension, cirrhosis, primary biliary cirrhosis
        • Pregnancy is difficult, Treating bleeding esophageal varices with nonselective beta-blockers, band ligation, and octreotide is safe and effective during pregnancy.
        • Ursodeoxycholic acid to be continued in PBC
      • Autoimmune hepatitis
        • Corticosteroids
        • Flare ups common
      • Wilson disease
        • Zinc is the agent of choice. D Pencillamin, trientere to be used in minimum possible dose
      • Chronic infection with hepatitis B or hepatitis C virus
        • Doesn’t need active therapy in Pregnancy
  • 37. Preexistent liver diseases
      • Portal hypertension, cirrhosis, primary biliary cirrhosis
        • Pregnancy is difficult, Treating bleeding esophageal varices with nonselective beta-blockers, band ligation, and octreotide is safe and effective during pregnancy.
        • Ursodeoxycholic acid to be continued in PBC
      • Autoimmune hepatitis
        • Corticosteroids
        • Flare ups common
      • Wilson disease
        • Zinc is the agent of choice. D Pencillamin, trientere to be used in minimum possible dose
      • Chronic infection with hepatitis B or hepatitis C virus
        • Doesn’t need active therapy in Pregnancy
  • 38. Liver diseases coincidental with but not induced by pregnancy
      • Acute viral hepatitis and other viral infections
      • Alcohol-related diseases
      • Gallstone disease
      • Budd-Chiari syndrome
  • 39. Viral Hepatits in Pregnancy Whats Different ?
    • Findings usually include fever, nausea, right upper quadrant pain, and markedly elevated transaminases (usually above 1000 IU/L)
    • Hepatitis A
      • The course of hepatitis A during pregnancy is generally similar to that in nonpregnant patients
      • Increased risk for premature labor
      • However, hospitalization may be indicated, specially during the last trimester and in the presence of severe anorexia, nausea, and vomiting .
  • 40.
    • Hepatitis B
      •   Acute infection with hepatitis B during pregnancy is not associated with increased mortality or teratogenicity.
      • Treatement with Lamivudine seems to decrease the transmission, however therapy during pregnancy is not indicated as of now. We can WAIT.
      • The risk of transmission is highest in mothers who are HBeAg - positive at the time of delivery
      • The administration of hyperimmune globulin and HBV vaccine protects 90% to 95% of infants from HBV infection .
  • 41.
    • Hepatitis C
      • The rate of vertical transmission of hepatitis C is less than 5%.
    • Hepatitis E
      • During pregnancy, HEV can cause fulminant hepatitis and can be a Medical Emergency. There is a significant mortality rate of 16-20% in pregnant women with acute HEV infection.
      • Fulminant hepatitis due to hepatitis E may resemble liver failure from acute fatty liver of pregnancy, hepatic infarction in the syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP), or herpes simplex hepatitis
      • Treatemnt is largely Supportive.
  • 42. Normal Pregnancy Viral Hepatitis H. Gravidarum IHCP HEELP AFLP S .Bilurubin Slightly down < or >5 AST Normal >1000 ALT Noraml >1000 ALP 3x in 3 rd timester Raised in choleststic ph S. Bile Acid Normal Nl or raised PT, INR Normal Normal S.Ammonia Normal Normal Total Count Normal Normal Platelets Normal Normal RBS Normal Normal S.Creatine Normal Normal LDH Normal Normal DIC No No
  • 43. Liver diseases induced by pregnancy
      • First trimester
        • Hyperemesis gravidarum
      • Second and third trimesters
        • Intrahepatic cholestasis of pregnancy
        • Preeclampsia, eclampsia, and the HELLP syndrome
        • Acute fatty liver of pregnancy
  • 44. Hyperemesis Gravidarum
    • Clinicaly
      • In First trimester
      • Severe, persistent nausea and vomiting
      • Mild jaundice, pruritis.
      • Can also Present with hypovolemia, dehydration,ketosis & electrolyte imbalance
    • 50% have increased LFTs (2-3x normal) seen 1-3 weeks after onset.
      • Enzymes elevated may be upto 1000.
      • Bilurubin elevates in severe cases
    • Resolves rapidly with cessation of emesis.
    • Negligible mortality .
  • 45. Normal Pregnancy Viral Hepatitis H. Gravidarum IHCP HEELP AFLP S .Bilurubin Slightly down < or >5 <5 AST Normal >1000 <500 ALT Noraml >1000 <500 ALP 3x in 3 rd timester Raised in choleststic ph Normal S. Bile Acid Normal Nl or raised Normal PT, INR Normal Normal Normal S.Ammonia Normal Normal Normal Total Count Normal Normal Normal Platelets Normal Normal Normal RBS Normal Normal Normal S.Creatine Normal Normal Normal LDH Normal Normal Normal DIC No No No
  • 46. Intrahepatic Cholestasis of Pregnancy
    • Incidence of 1 in 1,000-10,000 pregnancies
    • Seems to have a seasonal variation, peaking in November
    • Second and third trimester of pregnancy
  • 47. Pathogenesis
    • Cause is unknown
    • Evidence suggests both genetic and hormonal factors play a role
      • Genetic
        • The ABCB4 (adenosine triphosphate-binding cassette, subfamily B, member 4) , especially in a subtype of progressive familial intrahepatic cholestasis called PFIC3
      • Hormonal
        • Estrogen
        • Progesteron
  • 48. Clinical Manifestations
    • A pregnant lady in her 2 nd or 3 rd trimester
    • With pruritus more in palms, soles and face
    • Troubled more at night
    • With excoriations due to scrathing
    • May have excoriations due to scratching
    • She also gives a h/o of similar itching during previous pregnacny
    • And the fetus died inutero at that time !
  • 49. Clinical Manifestations
    • ~2 weeks after start of symptoms, jaundice develop in 50%
    • Accounts for 20-25% of cases of jaundice during pregnancy.
    • Jaundice is usually mild, but persists until delivery.
    • Symptoms usually abate about 2 days after delivery.
  • 50. Lab Investigations
    • ALP
      • increases 5-10 fold
    • Serum total bile acids
      • Serum total bile acid concentrations increase in ICP, and may be the first or only laboratory abnormality
    • Total bilirubin
      • mildly increased
    • AST, ALT
      • may increase mild to >1,000 U/L
  • 51. Lab Investigations
    • GGT
      • normal or slightly elevated
    • Coagulation factors
      • INR
        • usually normal
        • may be increased scondary to Vitamin K deficiency due to cholestasis or due to the use of bile acid sequestrants.
    • USG to rule out obstructive causes
  • 52. Normal Pregnancy Viral Hepatitis H. Gravidarum IHCP HEELP AFLP S .Bilurubin Slightly down < or >5 <5 <5 , direct AST Normal >1000 <500 <300 ALT Noraml >1000 <500 <300 ALP 3x in 3 rd timester Raised in choleststic ph Normal Elevated S. Bile Acid Normal Nl or raised Normal Raised PT, INR Normal Normal Normal Can be elevate S.Ammonia Normal Normal Normal Normal Total Count Normal Normal Normal Normal Platelets Normal Normal Normal Normal RBS Normal Normal Normal Normal S.Creatine Normal Normal Normal Normal LDH Normal Normal Normal Normal DIC No No No No
  • 53.
    • Treatement
      • U rsodeoxycholic acid 500 mg twice a day
      • Vitamin K
      • Cholestyramine
      • Benadryl, hydroxyzine and other antihistamines may help only slightly
      • Antihistamines may aggravate respiratory difficulties in preterm babies
    • Early delivery if fetal lung maturity is attained
  • 54.
    • The maternal prognosis in ICP is good . Affected women generally have no hepatic sequelae
    • Recurrence can occur
    • In contrast to the favorable prognosis for mothers, ICP carries significant risk for the fetus . The main complications are fetal prematurity, meconium stained amniotic fluid, intrauterine demise, and an increased risk for neonatal respiratory distress syndrome
  • 55. HELLP SYNDROME
  • 56. HELLP SYNDROME
    • The HELLP syndrome is a multi-system disease variant of severe preeclampsia that is characterized by microangiopathic hemolytic anemia (MAH), hepatic dysfunction (hepatic necrosis), thrombocytopenia (platelet count, <100,000/ mm3), and, in the syndrome ’ s most severe form, DIC.
  • 57. HELLP Syndrome
    • Third trimester
    • Incidence of 0.17-0.85%
    • Occurs in 20-25% of women with preeclampsia
    • 20% with HELLP have no HTN or proteinuria
    • ? Imbalance between vasoconstrictive and vasodilative forces causing endothelial dysfunction and platelet aggregation
  • 58. HELLP Syndrome
    • Presentation:
      • Mean age – 25 years
      • RUQ pain 70-90%
      • Nausea, vomiting common
      • Headache 25%
      • Visual changes 15-30%
      • Generalized edema 50-67%
      • Ascites 8-10%
  • 59. HELLP Syndrome
    • Lab Abnormalities
      • Low haptoglobin level in 95%
      • Bilirubin elevation 47-62%
      • Low platelets 50%
      • AST/ALT elevation (3x above normal)
  • 60. Normal Pregnancy Viral Hepatitis H. Gravidarum IHCP HEELP AFLP S .Bilurubin Slightly down < or >5 <5 <5 , direct <5 AST Normal >1000 <500 <300 >500 ALT Noraml >1000 <500 <300 >500 ALP 3x in 3 rd timester Raised in choleststic ph Normal Elevated Normal S. Bile Acid Normal Nl or raised Normal Raised Normal PT, INR Normal Normal Normal Can be elevate May be elevat S.Ammonia Normal Normal Normal Normal Normal Total Count Normal Normal Normal Normal Normal Platelets Normal Normal Normal Normal Low RBS Normal Normal Normal Normal Normal S.Creatine Normal Normal Normal Normal Usually Nl LDH Normal Normal Normal Normal Raised DIC No No No No Can Occur
  • 61. HELLP Syndrome
    • Maternal complications
      • DIC 4-38%
      • Placental abruption 10-16%
      • Acute renal failure 1-8%
      • Severe ascites 5-8%
      • Pulmonary edema 2-10%
      • ARDS 1%
      • Hepatic infarction / rupture 1%
  • 62. HELLP Syndrome
    • Management
      • Complete bed rest
      • Corticosteroids beneficial
      • Supportive therapy
        • Coagulopathy correction
        • Ventillatory Support
        • Dialysis
        • Platelet transfusion
    • Maternal mortality 8%
    • Fetal mortality 8-37%
  • 63. Treatement - HELLP
    • Removal of the chorionic villi by delivery is the only defenitive therapy
    • Severe maternal an indication for prompt delivery regardless of gestational age.
      • For pregnancies ≥ 34 weeks of gestation, delivery rather than expectant
      • For pregnancies less than 34 weeks of gestation in which maternal and fetal status is reassuring, delivery after a course of glucocorticoids to accelerate fetal pulmonary maturity rather than expectant management or prompt delivery.
      • For gestations less than 30 to 32 weeks with an unfavorable cervix, cesarean delivery to avoid a potentially long induction
  • 64. Treatement - HELLP
    • Correct coagulopathy if DIC is present
    • IV magnesium sulfate to prevent seizures
    • Provide treatment for severe hypertension to prevent stroke
    • Platelet transfusion
    • Consider Dexamthasone
      • Onset of DIC = immediate delivery
    • Be aware of the possiblity of subscapsular hematoma and rupture
      • Keep Blood ready
      • Surgical Interventions
  • 65. Acute Fatty Liver of Pregnancy
  • 66. Acute Fatty Liver of Pregnancy
    • Acute Yellow atrophy of liver
    • Characterized by microvesicular fatty infiltration of hepatocytes, is a disorder which is unique to human pregnancy.
    • True MEDICAL and OBSTRETICAL Emergency
    • 1 in 7000 to 1 in 20,000 deliveries
    • It is more common with multiple gestations and possibly in women who are underweight.
  • 67.
    • Acute fatty liver of pregnancy most frequently complicates the third trimester and is commonly associated (or complicated ) with preeclampsia (50 to 100 percent).
    • Acute fatty liver of pregnancy is similar histologically and clinically to Reye's syndrome and Jamaican vomiting sickness, both diseases of microvesicular fatty infiltration
    Riely CA. Hepatic disease in pregnancy. Am J Med 1994;96(1A):18S-22S 3. Samuels P, Cohen AW. Pregnancies complicated by liver disease and liver dysfunction. Obstet Gynecol Clin North Am 1992;19:745-63
  • 68. Clinical Manifestations
    • The duration of prodromal symptoms and signs is variable
    • Often presents with nausea and vomiting, followed by severe abdominal pain and headache
  • 69. Clinical Manifestations
    • The right upper quadrant is generally tender, but the liver is not enlarged to palpation
    • Within a few days, jaundice appears, and the patient becomes somnolent and eventually comatose
    • Hematemesis and spontaneous bleeding result when the patient develops hypoprothrombinemia and DIC
  • 70.
    • Vomiting 80
    • Abdominal pain 52
    • Jaundice 93
    • Encephalopathy 87
    • Polydipsia 80
    • Pruritus 60
    • Ascitis 47
  • 71. Clinical Manifestations
    • Oliguria, metabolic acidosis, and eventually anuria occur in approximately 50 percent of patients
    • Diabetes insipidus may also accompany the disease, but may not manifest itself until postpartum
    • These patients may respond to dDAVP after delivery
  • 72. Clinical Manifestations
    • If the disease is allowed to progress, labor begins and the patient delivers a stillborn infant
    • Uteroplacental insufficiency may be the cause of fetal distress and fetal death in these patients.
  • 73. Clinical Manifestations
    • During the immediate postpartum period, the mother becomes febrile, comatose and, without therapy, dies within a few days
    • DIC, renal failure, profound hypoglycemia, and occasionally pancreatitis are the most often cited immediate causes of death
  • 74. Pathogenesis
    • A genetic component has been suggested
    • Recent research suggests that AFLP is associated with a ln mutation in the long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD), a fatty acid β oxidation enzyme.
    • Preeclampsia is present in 50% or more of cases of AFLP and may play a role in its origin
    • Matern D, Hart P, Murtha AP, Vockley J, Gregersen N, Millington DS, et al. Acute fatty liver of pregnancy associated with short-chain acyl- coenzyme A dehydrogenase deficiency. J Pediatr 2001;138:585-8.   [76]. Brackett JC, Sims HF, Rinaldo P, et al. Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency. J Clin Invest 1995;95:2076-82.  
  • 75. Normal Pregnancy Viral Hepatitis H. Gravidarum IHCP HEELP AFLP S .Bilurubin Slightly down < or >5 <5 <5 , direct <5 <5 AST Normal >1000 <500 <300 >500 <500 ALT Noraml >1000 <500 <300 >500 <500 ALP 3x in 3 rd timester Raised in choleststic ph Normal Elevated Normal Normal S. Bile Acid Normal Nl or raised Normal Raised Normal Normal PT, INR Normal Normal Normal Can be elevate May be elevat Elevated S.Ammonia Normal Normal Normal Normal Normal Elevated Total Count Normal Normal Normal Normal Normal High Platelets Normal Normal Normal Normal Low Low RBS Normal Normal Normal Normal Normal Low S.Creatine Normal Normal Normal Normal Usually Nl Can be raised LDH Normal Normal Normal Normal Raised Raised or normal DIC No No No No Can Occur Yes
  • 76.
    • There is a large clinical overlap between AFLP and HELLP syndrome and it may be difficult, even impossible, to differentiate them. However, evidence of hepatic insufficiency such as hypoglycemia or encephalopathy are suggestive of AFLP.
    • Imaging tests are primarily used to exclude other diagnoses, such as an hepatic infarct or hematoma
  • 77. Liver Biopsy in AFLP
    • Liver biopsy is diagnostic, showing the characteristic picture which is the microvesicular fatty infiltration of the hepatocytes. The fat droplets surround centrally located nuclei, giving the cytoplasm a foamy appearance.
  • 78.
    • The primary treatment of acute fatty liver of pregnancy is prompt delivery
    • Treat complication
      • Correct coagulation
      • Correct Platelets
      • Mechanical Ventilation in Coma, Respiratory distress
      • Electrolytes
      • Dialysis in Renal Failure
      • Parentral Nutrition in Pancreatitis
    • Can Recurr in subsequens pregnancies
  • 79.
    • Thank you