Hepato&spleenomegaly

clinical correlation of HSM

1. HEPATO & SPLEENOMEGALY Dr.Subash Arun

2. HEPATOMEGALY : Enlargement of liver is called hepatomegaly . Presence of a palpable liver does not always represent hepatomegaly . May be mistaken for displacement of the liver by lung pathologies. abdominal tumor spinal deformity

3. The normal range for liver span at 1 week of age - 4.5 to 5 cm. At 5 yrs of age- 6 to 8 cms 12 years, boys - 7 to 9 cm girls - 6 to 8cm Procedure:

4. Surface markings : Upper border:4 th ICS in MCL Lower border:9 th ICS in MCL Lateral border:6 th rib in MAL

5. Functions of liver: Synthesis-albumin gluconeogenesis coagulation factors Metabolism-sugar proteins,fats Detoxification Storage-vitamin A( ito cells),B12 ,iron copper Protective-RES ( kuppfer cells)

6. Grades of hepatomegaly : mild- <4cms below Rt subCostal Margin. mod- 5-7cms “ “ mass- >7cms “ “

7. Hepatomegaly - five mechanisms, Infections, Excessive storage, Infiltration, Congestion, and Obstruction.

8. Liver E/o: 1, Edge/margin: sharp/ iregular – cirrhosis round with soft consistency- kwashiorkor. 2, Surface- smooth-congestion irregular- granular(portal cirrhosis) nodular(post necrotic cirrhosis) uneven- multiple hydatid cysts multiple liver abscess

9. 4, Consistency- Soft- CCF,acute hepatitis,anaemia Firm- Chronic active hepatitis, cirrhosis wilsons , galactosemia neonatal hepatitis. Hard- CML,hepatoblastoma Cystic- hemangioma

10. 5, Tenderness: is seen in acute enlargement of liver due to stretching of Glisson’s capsule. in c/o cirrhosis or malignancy it will be tender when capsule is infiltrated . localised tenderness is seen in c/o abscess/infected cyst.

11. Causes of tender hepatomegaly : Infective- viral hepatitis, infectious mononucleosis leptospirosis amoebiasis congestive- CCF Budd- chiari synd misc- hepatoma,hydatid cyst

12. 6, Pulsations: s/I A-V malformations triscupid regurgitation(systolic) tricuspid stenosis (diastolic) aortic regurgitation( Rosenbach sign)

13. Palpable findings of liver: soft,smooth,tender,enlarged CCF firm & nodular cirrhosis of liver obst jaundice nodular secondaries,hepatoma Riedels lobe tongue like projection of rt lobe of liver

14. General e/o findings in c/o hepatomegaly : Hair flag sign(kwashiorkor) Head microcephaly ( cong.rubella ) hydrocephalus(toxoplasmosis) craniotabes ( hypervitaminosis A) Eyes cataract ( wilsons,galactosemia ) KF ring( wilsons ) Hazy cornea(hurler)

15. PALLOR – 1) Infections - Malaria, kala-azar , bacteremia 2) Haemolytic anaemia - Hereditary spherocytosis , sickle cell anaemia , thalassaemia , autoimmune haemolytic anaemia . 3) Nutritional - Iron deficiency anaemia . 4) Leukaemia and lymphomas

16. Fever - Infection - Malaria, kala-azar , enteric fever, malignancy Jaundice, anorexia, vomiting, haematemesis , malena - liver disease especially cirrhosis with portal hypertension Recurrent Jaundice - Liver disease, Hemolytic anemia Dyspnoea / difficulty in feeding - cardiac causes e.g. CCF

17. Petechiae , purpura , ecchymosis , lymphadenopathy etc. – Leukaemia Koilonychia , platynychia - Iron deficiency Mental retardation - Mucopolysaccharoidoses

18. Neck engorged veins,raised jvp (constrictive pericarditis ) Chest spider naevi,gynecomastia (liver failure) Skin scratch marks( cholestasis )

19. CNS tremors & dystonia ( wilsons ds ) Mental retardation(glycogen storage ds ) Skeletal rickets,cystinosis,tyrosinemia . Delayed development - Carbohydrate / Lipid storage disorders

20. Abdomen E/o: Firm consistency liver with sharp edge - Cirrhosis, constrictive pericarditis Just palpable soft spleen - Enteric fever, infective endocarditis , etc. Ascites - Suggests cirrhosis with portal hypertension, malignancy, TB

21. HISTORY: Age at onset Sex Fever, jaundice Acute illness, dyspnea , fatigue, diarrhea, vomiting Signs of malignancy- proptosis , subcutaneous nodules Travel history – endemic diseases Developmental milestones Nutrition history (neonatal formula) Medical history: umbilical catheter, weight loss, failure to thrive, bleeding, bruising, Pruritis , pallor, heart disease , rashes, joint pain. Family history: Early cholecystectomy , gallstones, anemias , ethnic heritage, liver disease, maternal HBV, HCV

22. Age Neonates and first few months of life - e.g. Haemolytic anaemias ( Thalassaemia major), storage disorders Any age - Malaria, kala azar , sepsis, enteric fever, etc.

23. INVESTIGATIONS Complete haemogram - Infections, anaemia Peripheral smear - Leukaemia ( Blast cells ) Thalassaemia ( hypochromia , nucleated RBC's, target cells ) Sickle cell anaemia ( sickling on treatment with 2% sodium metabisulphite ) Parasitic diseases ( Eosinophilia ) ESR - Elevated in inflammatory diseases Reticulocyte count - High in haemolytic anaemia

24. Liver Function Test Serum proteins - Low in kwashiorkor SGOT/SGPT - Raised in hepatitis & hepatic necrosis Alkaline phosphatase - Elevated in hepatobiliary obstruction & liver abscess Bilirubin (total, direct) - Haemolytic anaemias

25. MISCELLANEOUS TESTS Raised alpha foeto protein- Hepatoblastoma Hbs Ag - Hepatitis B High prothrombin time - Liver parenchymal dysfunction High sweat chlorides - Cystic fibrosis Wilson's disease - Low ceruloplasmin Liver scan - To differentiate biliary atresia from neonatal hepatitis Urine and stool examination - In case of jaundice

26. USG abdomen - Cirrhosis with portal hypertension, Ascites , Tumors & cysts Liver biopsy- Pathological diagnosis Chest X-ray - ECG, echocardiography if cardiac cause suspected Haemolytic profile in suspected haemolytic anaemia Blood culture, Widal , Mantoux test - as required

27. Approach to child with hepatomegaly

28. Approach to neonate with hepatomegaly

29. TREATMENT STRATEGIES Therapy is directed at treatment of underlying disease Infections – Consider interferon for hepatitis B – Consider interferon and ribavarin for hepatitis C Metabolic disease – Metabolism consultation – Often requires specific restricted formulas Cholestasis – Ursodeoxycholic acid – Supplemental fat soluble vitamins A, D, E, K

30. Immune suppression for autoimmune hepatitis Chemotherapy – Histiocytosis , leukemia, lymphoma Surgical treatment Kasai portoenterostomy for biliary atresia has better outcome if done before 60 days of age

31. CASE HISTORY A three years old first order female child Born out of 2 nd degree consanguineous marriage

32. presented with chief complaint of Distension of abdomen since 4months of age. No h/o: Jaundice, edema Change in bowel pattern , weight loss Past h/o:at 4 months of age child developed convulsions- fever

33. vomiting, Altered sensorium Breathlessness Subsequently she had 8-10 admissions for severe metabolic acidosis , with hypoglycaemia Birth history: Full term, normal delivered

34. Development history : Sat without support at the age of 1 year Walked unassisted at the age of 2 years On examination: Weight : 14 kg; Height: 84 cm (< 3 rd percentile) Doll like face, protuberant abdomen No pallor, cyanosis, clubbing, lymphadenopathy , icterus

35. P/A: huge hepatomegaly almost reaching right lower quadrant; no splenomegaly CNS: Normal muscle tone and power, normal deep tendon reflexes Other systems: NAD Fundus : NAD

36. Attending paediatrician may have following questions: Differential diagnosis? Is this is a routine chronic liver disease? Am I dealing with GSD or fatty oxidation disorder where we get hypoglycaemia, Hepatomegaly , and metabolic acidosis

37. How will I explain acidosis? What is my diagnosis here? How should I investigate this case further?

38. APPROACH TO A CHILD WITH HEPATOMEGALY Let me examine him fully before I can say that this person is dead !!

39. First be sure it is hepatomegaly and not a pushed down liver !!!! Always assess Liver span Consistency Surface

40. APPROACH TO A CHILD WITH HEPATOMEGALY In this particular case one may just consider SIZE of the liver which was huge. Very limited causes of huge hepatomegaly at this age. Most likely is some kind of storage disorder; GSD, LSD or stretching a little bit FAOD.

41. APPROACH TO A CHILD WITH HEPATOMEGALY Presence of hypoglycemia and severe metabolic acidosis will further reduce the differential diagnosis to GSD and FAOD

42. APPROACH TO A CHILD WITH HEPATOMEGALY On the other hand, if size of the liver is moderate or mild , differential diagnoses could be altogether different. Since there could be many causes to consider; good history and physical examinaton are very essential

43. Keep in mind that Wilson’s disease could have an acute presentation. Chronic liver disease may have acute decompensation

44. RULE OF THUMB ??? Huge hepatomegaly with preserved liver functions suggests storage disorder; at any age; or Reticuloendothelial hyperplasia

45. INVESTIGATIONS Remember!! Good history, aided by meticulous examination will give clue to the underlying cause, more than any single investigation Let me see if I can find out what is wrong with you!!

46. Liver biopsy showing mosaic pattern, prominent cell membranes and nuclear hyperglycogenation (HE stain); Distended hepatocytes without fibrosis

47. FINAL DIAGNOSIS GLYCOGEN STORAGE DISORDER TYPE 1

48. A diagnostic approach to splenomegaly

49. SPLEENOMEGALY It refers to enlargement of spleen beyond its normal size. A spleen is said to be significantly enlarged if it is palpable atleast 1cm below costal margin in a child more than 6months of age. In 30% of newborns & 15% of infants <6months palpable spleen is a normal variant.

50. Anatomy It lies within the left upper quadrant of the peritoneal cavity.  Abuts ribs 9-11, the stomach, the left kidney, the splenic flexure of the colon, and the tail of the pancreas.  

51. Anatomy Normal Spleen Autopsy: <250g. Radioisotope Scintiscan : 12cm long x 7cm wide. Ultrasound: 11cm cephalocaudad diameter. ~3% of healthy people have splenomegaly .

52. Splenomegaly Poulin et al defined splenomegaly on the basis of size of spleen Moderate; if the largest dimension is 11-20 cm. severe; if the largest dimension is greater than 20 cm.

53. Splenomegaly Splenomegaly definition by weight MILD; Spleens weighing 400-500 g . Moderate; Spleen weighing 750-1000g. Massive; More than 1000 g to indicate massive splenomegaly .

54. Functions of spleen: Reservior for platelets,monocytes,FVIII etc. Haematopoiesis in fetus . Repairs and destruction of RBC’s by culling & pitting. PITTING removal of inclusion bodies ( heinz bodies,howell jolly bodies) without destroying RBC’s. CULLING removal of damaged/old RBC’s from circulation.

55. Immune function : IgM , properidin,tuftsin are produced by spleen. prevention of inf. By capsulated org.( H.influ etc) role in phagocytosis .

56. Grading of spleenomegaly : Grade 1-normal,not palpable even on deep inspiration. Grade 2-palpable just below costal margin usually on deep inspiration. Grade 3-palpable below costal margin but not projected beyond a horizontal line half way b/w costal margin and umblicus.the projection need to be ascertained along a line dropped vertically from the left nipple.

57. Grade 4- lowest palpable point approaching the umblical level but not below a line drawn horizontally through umblicus . Grade 5-lowest palpable point below umblical level but not projected beyond a horizontal line situated halfway b/w umblicus and symphysis pubis. Grade 6-lowest palpable point beyond lower limit of grade 5.

58. Grading according to size of spleen below LCM : MILD  palpable <3cms below LCM MODERATE  4-7 below LCM SEVERE >7cms below LCM.

59. Clinical E/o : Size & Degree : it usually enlarges towards RIF. it is measured as child takes a deep breath from a point on LCM in MCL to the tip of the enlarged spleen. Margin: Splenic notch is felt on the Ant. border & has a sharp margin. Diff from kidney where there is absence of notch & margin is round

60. Spleen vs. Kidney Spleen Splenic notch. Can cross midline. Can’t get above. Moves down on inspiration. Not ballotable . Splenic rub. Kidney No notch. Never cross the midline. May get above. Doesn’t move with respiration. Ballotable . No rub.

61. Inspection Look in left Hypochondrium. Examination of the Spleen

62. Percussion of spleen Normal Left midaxillary line 9 th –11 th intercostal space width 4-7cm. Enlargement of splenic dullness: splenomegaly.

63. Percussion (3 methods): Percussion of Traube's Space boundaries – Left anterior axillary line 6th rib costal margin . This area should be resonant on percussion. Dullness indicates possible splenic enlargement

64. Percussion by Castell’s method : percuss in the lowest Left intercostal space in the anterior axillary line (usually the 8th or 9th IC space) this space should remain resonant during full inspiration . dullness on full inspiration indicates possible splenic enlargement (a positive Castell’s sign)

65. Percussion by Nixon’s method : place the patient in Right lateral decubitus begin percussion midway along the Left costal margin proceed in a line perpendicular to the Left costal margin if the upper limit of dullness extends >8 cm above the Left costal margin, this indicates possible splenomegaly

66. Palpation of spleen To palpate the spleen, the patient is in the supine position with the knees flexed to decrease abdominal muscle tone. Begin the examination by palpating the right lower quadrant and move upward across the abdomen as the patient.

67. Palpation (3 methods) Method #1: begin palpation in the RLQ. direct the patient's breathing by telling them when to take a deep breath and when to exhale while proceeding diagonally towards the Left Upper Quadrant (LUQ), try to palpate the spleen edge during each inspiratory phase

68. Method #2: place the patient’s Left fist under their Left posterior chest. With your Right hand, begin palpation in the RLQ. Direct the patient's breathing by telling them when to take a deep breath and when to exhale while proceeding diagonally towards the LUQ, try to palpate the spleen edge during each inspiratory phase

69. Method #3 –The Hooking maneuver of Middleton (optional): Place the patient’s Left fist under their Left posterior chest position yourself on the patient’s Left side, facing the patient’s feet. Using both hands, curl your fingers under the patient’s Left costal margin ask the patient to take a long, deep breath à attempt to palpate the spleen with your fingertips

70. Percussion of spleen Percussion is also used to delineate the size of the spleen . Percussion is only approximately 60% accurate in most studies, with palpation about 50% accurate.

71. Consistency: soft  1, normal 2,septicemia 3,enteric fever 4,infectious mononucleosis firm 1,cirrhosis 2,lymphoma 3,leukemia 4,chr.malaria hard secondaries

72. Tenderness: s/I  infective endocarditis splenic abscess splenic infarction Surface: smooth  congestive causes like portal HTN irregularhydatid cyst

73. Spleen moves downwards and medially during inspiration. Fingers cannot be insinuated btw enlarged spleen and LCM Spleenic rub is palpable in spleenitis

74. Mechanism of splenomegaly : Reactive Reticulo -endothelial hyperplasia Lymphoid hyperplasia Proliferation of lymphoma cells Infiltration by abnormal cells Extramedullary hemopoeisis Proliferation of macrophages d/t RBC destruction Vascular congestion

75. Symptoms and signs Abdominal pain/tiredness . Early satiety due to splenic encroachment . Symptoms of anemia due to accompanying cytopenia . Febrile illness (infectious). Pallor, dyspnea , bruising, and/or petechiae (hemolytic process).

76. Symptoms and signs History of liver disease (congestive ). Weight loss, constitutional symptoms ( neoplastic ). Pancreatitis ( splenic vein thrombosis). Alcoholism, hepatitis (cirrhosis).

77. Signs Palpable left upper quadrant abdominal mass . Splenic rub . Lymphadenopathy .

78. Symptoms and signs Signs of cirrhosis ( eg , asterixis , jaundice, telangiectasias , gynecomastia , caput medusa, ascites ). Heart murmur ( endocarditis , congestive failure). Jaundice ( spherocytosis , cirrhosis). Petechiae (any cause of thrombocytopenia ).

79. Causes of splenomegaly Infective Hyperplastic Congestive Infiltration

80. infective Acute & subacute - IMN, infective endocarditis , severe pyogenic inf. Viral hepatitis,CMV,AIDS Chronic - TB,syphilis,brucellosis Tropical splenomegaly Malaria,kala azar , trypanosomiasis

81. congestive Intra hepatic obst.portal hypertension - cirrhosis,biliary cirrhosis,hemochromatosis - primary sclerosing cholangitis Extra-hepatic portal hypertension - venous malf,thrombosis,stenosis - ext.occlusion of portal,splenic vein Chronic passive congestion of cardiac origin

82. hyperplastic Extramedullary hemopoeisis - myeloprolif.d /s - marrow damage - marrow infiltration Reticulo endothelial hyperplasia –(abn.RBC) - sickle cell d/ s,spherocytosis,Hbnopathies , thalassemia major,PNH

83. infiltrative Malignant infiltration- CML,lymphoblastic - lymhomas , MPD, - angiosarcoma,tumors - metastasis (melanoma) benign - - storage d/s – Gaucher’s,Neiman -pick - amyloidosis - hurler’s syndrome,MPS - cysts,fibromas,hemangiomas,hamartomas - Eosnophilic granulomas

84. Disordered immunoregulation Felty’s syndrome- RA+ splenomegaly+leucopenia Systemic lupus erythromatosis Collagen vascular diseases Sarcoidosis Immune thrombocytopenia

85. Splenomegaly in children Metastatic neuroblastoma . Infection . Autoimmune: juvenile rheumatoid arthritis . Haemolysis : hereditary spherocytosis , sickle cell anaemia , Thalassaemia Neoplasia : ALL, Hodgkin disease and NHL, acute or chronic myeloblastic leukemia, neuroblastoma . Inherited diseases: Gaucher's disease and other storage disorders.

86. Massive splenomegaly (>8cm >1000gm) Myeloproliferative disorder Chronic malaria,kala-azar (trop. Splenomegaly ) Storage disorders Thalassemia major Sarcoidosis Hairy cell leukemia Gaucher disease Diffuse splenic hemangiomatosis

87. Moderate splenomegaly (4-8cm ) Cirrhosis Lymphomas‘ Amyloid Splenic abscess,infarct Hemolytic anemias IMN

88. Mild splenomegaly (1-3cm) Acute infective conditons Acute malaria,tyhoid,kala-azar,septicemias

89. Special situations associated with splenomegaly Fever - typhoid,malaria,kalaazar , infect.endocarditis , leukemia,lymphoma Tender spleen- rupture,abscess,infarct a/c illness+ anemia- AIHA,leukemia Fever + LN- IMN,leukemia,lymhomas,SLE,sarcoid Anemia - hemolytic anemia,hemoglobinopathies Jaundice – cirrhosis,hemolytic anemia Pulsatile spleen- aneurysm High ESR- connective tissue disorder Leukopenia - felty’s syndrome,septicemia

90. Step-wise approach to splenomegaly History Physical examination Laboratory testings Imaging Specialised testing

91. history Age ,gender Race h/o recent infections like malaria Fever,weight loss,sweating ( lymphomas,infections ) Pruritis Abnormal bleeding/bruising Joint pain h/o alcholism h/o trauma h/o neonatal umblical sepsis Residence & travel abroad

92. History …..cont Jaundice High risk sexual behavior (AIDS) Past medical history Drugs

93. Physical examination Size of the spleen Hepatomegaly Lymphadenopathy Fever Icterus Bruising,petechiae Oral & supf.sepsis Stigmata of liver disease Stigmata of RA/SLE Splinter hemorrhage,retinal hemorrhage Cardiac murmurs

94. Lab investigations CBC Blood smear Retic count Blood C/S Serology ( fungal,viral,parasitic ) LFT Hb electropheresis / coombs test Coag.profile Amylase/lipase AMA, Anti CCP,RA factor Bone marrow analysis

95. Hypersplenism Criteria for a diagnosis of hypersplenism : anemia . Leukopenia . Thrombocytopenia. combinations thereof, plus cellular bone marrow, splenomegaly , and improvement after splenectomy .

96. Approach to Splenomegaly Depends on Pretest Probability Clinical Suspicion of Splenomegaly (>10 %). Percuss first and if positive palpate . If percussion is negative and suspicious, order an ultrasound . If percussion positive but palpation is negative, order an ultrasound . Both percussion and palpation positive = SPLENOMEGALY .

97. Diagnostic Approach CBC provides information about hematological, infectious, and inflammatory processes. Finding of pancytopenia , Anemia, Leukopenia , Thrombocytopenia may indicate bone marrow dysfunction or portal hypertension with hypersplenism .

98. Laboratory tests Routine tests : CBC, platelet count, sedimentation rate . chemistry panel, febrile agglutinins, serum haptoglobins , ANA test, Monospot test, serum protein electrophoresis, tuberculin test . chest x-ray, EKG, and flat plate of the abdomen.

99. Diagnostic Approach Increased sedimentation rate suggests infectious, inflammatory, or neoplastic process. Bacterial, fungal, and other cultures may be performed with suspected infection.

100. Diagnostic Approach Bone marrow exam is useful in diagnosis of histiocytoses , lysosomal storage disorders, and some infections(e.g., disseminated histoplasmosis ).

101. Diagnostic Approach Liver function tests and abdominalU /S with Doppler methods should be performed with suspected portal hypertension. Abdominal U/S and CT locate and define extent of splenic masses

102. If there is jaundice A hepatitis profile, red cell fragility test, and blood smear for parasites should be done. If there is fever. Serial blood cultures, leptospirosis antibody titer, and smear for malarial parasites should be done. Laboratory tests

103. Laboratory tests If there is a petechial rash A coagulation profile should be done. To rule out malignancies Lymph node biopsies and bone marrow examinations may be necessary.

104. Imaging USG - sensitive & specific non-invasive CT scan – etiology of splenomegaly - liver size,heterogenecity - splenic mets , abscess,calcf.,cysts - retro peritoneal LN - craniocaudal ln > 10 cm Liver - spleen colloid scan- (RBC –Cr51,Tc99) - hepatic steatosis,SOL,splenic functions - PHT,colloid shift + MRI/ Doppler usg - portal/ splenic vein thrombosis - cavernomas

105. imaging MRI scan- liver hemangiomas hemochromatosis erlenmeyer flask sign( Gaucher ) PET scan - Dx & staging of lymphomas - determine metabolic cells in spleen

106. Imaging Studies Splenoportography This modality is used to evaluate portal vein patency and the distribution of collateral vessels before shunt operations for cirrhosis. Findings can help identify the cause of idiopathic splenomegaly , especially in children . Angiography : Angiographic findings are used to differentiate splenic cysts from other splenic tumors .

107. Imaging Studies Liver-spleen colloid scanning Erythrocytes are labeled with chromium-51 ( 51 Cr) , mercury-197 ( 197 Hg), rubidium-81 ( 81 Rb ), or technetium-99m ( 99m Tc ), and the cells are altered by treatment with heat, antibody, chemicals, or metal ions so that the spleen sequesters them after infusion. A spleen length >14 cm is consider enlarged on liver-spleen scan

108. Specialised testing Abd.fat pad aspiration- amyloidosis JAK-2 mutation Gene testing( bcr-abl ,C282Y)-leukemia Enzyme testing-storage Lymph node biopsy- infection,malignancy FNAB spleen Splenectomy-hyperspleenism Lung or skin biopsy Liver biopsy

109. summary Splenomegaly – major physical finding Step wise approach- history,physical exam Look for associated features Lab investigation & Imaging Search for etiology & treat

110. References: 1,Gupte S. Differential Diagnosis in Pediatrics, 5 th edn Nw Delhi: Jaypee 2008. 2,Nelson text book of pediatrics - 20 th edn .