Jaundice
Splenomegaly
Hepatomegaly
Edema
Real Big Brain stuff
100

Define Jaundice 

(double points for values exact values) 


Definition-Jaundice, the yellow discoloration of skin and sclerae, results when the serum level of bilirubin, a pigmented compound, is elevated. Jaundice is not evident until the total serum bilirubin is at least 2–2.5 mg/dL in children out of the neonatal period

100

Causes of Splenomegaly

Causes of Asplenia

Causes of Splenomegaly-

Infective- Malaria, infective endocarditis

Malignancy- CLL, Leukemia, Lymphoma

Hematological- Pernicious anemia, Hemolytic anemia


Causes of Asplenia- Asplenia refers to complete loss of function of the spleen and may be anatomic or functional. 

Anatomic asplenia is most often due to surgical splenectomy, performed for trauma or therapeutically (eg, for hemolytic anemias or immune thrombocytopenia) . 

Functional asplenia refers to complete loss of function caused by medical conditions and occurs most frequently with sickle cell anemia 

100

Causes of hepatomegaly

double points for grouping

Infection: EBV, hepatitis, malaria
Hematological: leukemia, lymphoma, SCD, Beta thalassemia, G6PD deficiency
Biliary: PBC, PSC, biliary atresia
Nutritional: kwashiorkor
Cardiac: RHF, TR, Budd-Chiari syndrome (hepatic vein obstruction)
Neoplastic: Primary/Metastatic disease
Infiltrative: Fatty liver disease, haemochromatosis, sarcoidosis, amyloidosis
Storage liver disease: Reye syndrome, mucopolysaccharidosis
Wilson disease, glycogen storage diseases, alpha-1-antitrypsin

100

Edema Definition

  • Edema: abnormal fluid accumulation in the interstitium due to an imbalance in fluid homeostasis caused by either decreased absorption or increased secretion of fluid in the interstitium
100

Causes for Bilateral and Unilateral enlarged Kidneys

Biilateral- APKD, Bilateral Hydronephrosis, Amyloidosis

Unilateral- Hydronephrosis, Renal Cancer, Renal cyst

200

What are some causes of Jaundice (group them hehe)

 unconjugated hyperbilirubinemia

  • Hemolytic
  • ↑ Production of bilirubin
  • Hemolytic disease of the newborn (e.g., ABO incompatibility, Rh incompatibility) 
  • Erythrocyte enzyme defects (e.g., G6PD deficiency, pyruvate kinase deficiency)
  • Erythrocyte membrane defects (e.g., hereditary spherocytosis)
  • Hemoglobinopathies (e.g., sickle cell anemia, thalassemias)
  • Hematomas (e.g., vacuum-assisted delivery, vitamin K deficiency bleeding) 
  • Infection/sepsis (see “Neonatal infection”)
  • Polycythemia
  • Nonhemolytic
  • ↓ Conjugation of bilirubin
  • Gilbert syndrome
  • Crigler-Najjar syndrome
  • Deficiency of UDP-glucuronosyltransferase
  • Hypothyroidism
  • Decreased stool passage → ↑ Enterohepatic circulation of bilirubin
  • GI obstruction (e.g., pyloric stenosis, bowel obstruction)
  • Hirschsprung disease
  • Cystic fibrosis
  • Breast milk jaundice
  • Breastfeeding jaundice
  • Malnutrition

Pathological conjugated hyperbilirubinemia

  • Intrahepatic
  • ↓ Hepatic uptake of bilirubin
  • Rotor syndrome [3]
  • ↓ Excretion of bilirubin
  • Alagille syndrome [4]
  • TORCH infections
  • Dubin-Johnson syndrome [3]
  • Sepsis
  • Idiopathic neonatal hepatitis
  • Alpha-1-antitrypsin deficiency
  • Cystic fibrosis 
  • Galactosemia
  • Hypothyroidism
  • Medication
  • Extrahepatic
  • Biliary atresia
  • Biliary/choledochal cyst
  • Tumors/strictures

Mixed hyperbilirubinemia

  • Combined
  • Both conjugated and unconjugated hyperbilirubinemia occur
  • Hepatitis
  • Cirrhosis
200

investigations for Splenomegaly

Hemolysis -CBC, reticulocyte count, blood smear, serum bilirubin measurement, Coombs test, osmotic fragility study, RBC enzyme assays, hemoglobin electrophoresis

 Infection -CBC, differential, blood cultures, viral studies (EBV, CMV, HIV), toxoplasmosis, Bartonella titers, TB test, malaria blood smear, PCR testing and/or blood smear for babesiosis, CRP, procalcitonin

 Liver disease-Liver function tests, albumin measurement, prothrombin time, α1-antitrypsin, serum copper, ceruloplasmin

Portal hypertension Liver function tests; albumin measurement; prothrombin time; ultrasonography/CT of portal veins, liver, and spleen

 Immunologic and inflammatory disease ESR, CRP, C3, C4, antinuclear antibody, rheumatoid factor measurements; ferritin, urinalysis; BUN, serum creatinine, and immunoglobulin measurements

 Infiltrative disease CT, enzyme assay for Gaucher disease, tests as indicated for other storage diseases

 Malignancy CBC with differential, peripheral smear, CXR, uric acid, LDH, CT, bone marrow aspiration

 Genetic syndrome Molecular DNA testing or whole exome sequencing

200

Name 3 congenital infections responsible 

CMV, Rubella, Syphilis

200

Causes of Ascites (transudative vs exudative)


Bonus points if you can name medications that can cause edema


Transudate: CLD, CCF, volume overload, hypoalbuminemia, constrictive pericarditis

Exudate:
Infection - TB, pyogenic infection
Infarction
Inflammation - pancreatitis
Malignancy - luminal, pancreas, liver, ovarian, lymphoma
Other - Lymphoedema, hypothyroidism


The following list includes medications that commonly cause edema. It is not exhaustive.

  • Antihypertensives
    • Calcium channel blockers, especially dihydropyridines
    • Beta blockers
    • Clonidine
    • Hydralazine
    • Methyldopa
  • Gabapentinoids
  • Hormones
    • Corticosteroids
  • Chemotherapy
    • Docetaxel
    • Gemcitabine
    • Pemetrexed
    • Lenalidomide, thalidomide
    • Anticancer immunotherapy
  • NSAIDs
  • Thiazolidinediones
  • MAO inhibitors
  • Pramipexole
200

All or nothing G6PD, Hereditary Spherocytosis, 

G6PD

Glucose-6-phosphate dehydrogenase (G6PD) deficiency leads to an impaired regeneration of reduced glutathione, an important antioxidant, which makes RBCs more susceptible to oxidative stress and can result in episodic hemolytic anemia. this disorder is X Linked Recessive

  • Causes of increased oxidative stress are triggers of hemolytic crisis and include:
    • Fava beans
    • Drugs: antimalarial drugs (e.g., chloroquine, primaquine), sulfa drugs (e.g., trimethoprim-sulfamethoxazole), nitrofurantoin, isoniazid, dapsone, NSAIDs, ciprofloxacin, chloramphenicol
    • Bacterial and viral infections (most common cause): Severe enzymatic deficiency can inhibit respiratory burst activity due to reduced NADPH production in phagocytes. 
    • Inflammation: During an inflammatory reaction free radicals are produced and can diffuse into RBCs.
    • Metabolic acidosis




SPHEROCYTOSIS

An Autosomal-dominant hemoglobinopathy characterised by  molecular defects in membrane proteins of the RBC cytoskeleton, most commonly spectrin or ankyrin, giving the cells their characteristic shere shape.

• Reduction in surface-to-volume ratio causes spherocytes that are osmotically fragile and trapped by the spleen 

Clinical presentation • Neonatal period: Jaundice and hyperbilirubinemia sufficient to require exchange transfusion • Variably symptomatic based on severity • Anemia – Pallor, fatigue, exercise intolerance • Splenomegaly • Pigment gallstones at a young age • Susceptible to aplastic crisis as a result of parvovirus B19 infections – Erythroid marrow failure may result rapidly in profound anemia, high cardiac output failure, hypoxia, cardiovascular collapse; may have thrombocytopenia

  • Non-surgical treatments
    • Phototherapy and/or exchange transfusions may be necessary in neonates (e.g., to avoid kernicterus).
    • Blood transfusions may be required in cases of aplastic or hemolytic crisis (see “Complications” below).
    • Folic acid supplementation to maintain erythropoiesis
  • Splenectomy
    • Sole definitive treatment 
    • Prior to the procedure, vaccinate against Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitidis (see asplenia).





300

Investigations and Management of Jaundice

Investigations

  • Bilirubin tests  
    • Transcutaneous bilirubin measurement (TcB) 
      • Bilirubin levels > 95thpercentile on nomogram indicate neonates at high risk for developing neurological sequelae.  
    • Serum bilirubin measurement 
      • Total serum bilirubin measured
      • Differentiation of direct (conjugated) and indirect (unconjugated) bilirubin
  • Other laboratory tests 
    • Complete blood count (including reticulocyte count)
    • Blood group
    • Direct and indirect Coombs' test 
    • Markers of inflammation
    • Liver enzymes 
    • Total serum protein and serum albumin 
    • TSH and free T4 
    • G6PD activity (in patients with G6PD deficiency) 


Management

Management of jaundice 

-Full history e.g. medications, family history, overseas travel, past blood transfusions, jaundice contacts, pale stools, or dark urine (cholestasis).

-Examination Vital signs; conscious level (hepatic coma); hepatic stigmata (= chronic liver disease); pallor (haemolysis); hepatomegaly; splenomegaly; ascites; peripheral oedema. 

Treatment 

• Remove or treat underlying cause. 

• Stop bilirubin rising to level that may cause kernicterus 

• Treat any underlying cause, e.g. sepsis. 

• Start ‘blue light’ phototherapy (converts bilirubin to water-soluble form that can then be excreted in urine). 

• Use age/gestation specific charts to determine level to start phototherapy (see Fig. 6.2). Be aware of risk factors (family history, exclusive breast feeding, Rh or blood group incompatibility). 

• Measure SBR frequently (4–24-hourly depending on circumstances) and stop when falls below treatment level. 

• Ensure adequate hydration. 

• Cover eyes (phototherapy side effects: d or i temperature; eye damage; diarrhoea; dehydration; rash; separation from mother). 

• Exchange transfusion ± intravenous immunoglobulin (IVIG) if very high SBR (e.g. >450µmol/L in term infant at 48hr) or rapid rise (>8.5µmol/L/hr).  

300

Management and indications of Splenomegaly

(bonus points for post splenectomy management and management of  splenic sequestration (be sure to define splenic sequestration))

Medical Management 

- complete history and physical examination. 

-treat the underlying condition (treat viral infections, myeloproliferative disorders can be treated with chemotheraputic agents)


Symptomatic Treatment

-Pain Management


Surgical intervention

-splenectomy- for severe hypersplenism with the risk for rupture

-partial splenectomy



Preventive Care Post-Splenectomy

  • Vaccinations: Patients should receive vaccinations against pneumococcus, Haemophilus influenzae type b, and meningococcus prior to splenectomy and periodically thereafter to reduce the risk of infections.
  • Antibiotic Prophylaxis: Long-term antibiotic prophylaxis may be recommended to prevent bacterial infections in patients who have undergone splenectomy.

Splenic sequestration management- 

  • Acute management
    • Immediate IV fluid resuscitation for hypovolemia
    • Simple RBC transfusion in consultation with a sickle cell expert (avoid raising hemoglobin > 8 g/dL) 
  • Long-term management
    • Patients/caregivers should be taught to monitor spleen size to detect recurrence early.
    • Splenectomy or partial splenectomy may be indicated (e.g., for hypersplenism or life-threatening or recurrent sequestration events)
300

Investigations for liver dysfunction 

extra points for specific tests for etiology

• CBC • Reticulocyte count • Comprehensive metabolic panel • Fractionated bilirubin • ESR • Gamma-glutamyl transpeptidase • PT 

Specific test for etiology of liver dysfunction

• Hepatitis serologies A, B, and C • Alpha-1-antitrypsin • Alpha-fetoprotein • Serum ceruloplasmin • Antinuclear antibodies • Antismooth muscle antibodies • Anti-liver/kidney microsomal antibodies • Sweat chloride • Serum lipid profile

300

Investigations for edema

Obtain as indicated to evaluate for systemic causes of peripheral edema.

  • CMP: liver and/or kidney disease
  • TFTs: hyperthyroidism or hypothyroidism
  • BNP: heart failure
  • Urine protein/creatinine ratio: proteinuria and nephrotic syndrome

Imaging

  • Duplex ultrasound (preferred)
  • Allows for viewing of venous anatomy, patency, and valve function
  • Indications
    • Suspected DVT in patients with intermediate or high PTP, or low PTP with positive D-dimer
    • Lower extremity edema with negative workup for other causes
  • CT or MRI with contrast: if additional imaging is required after duplex ultrasound
  • Venography with intravascular ultrasound
    • If previous imaging was inconclusive
    • Also used for endovascular treatments
  • Lymphoscintigraphy: if lymphedema diagnosis remains uncertain after clinical evaluation
300

Why is Hypothyroidism in neonates associated with jaundice

The activity of uridine diphosphate glucuronyl transferase (UGT) in neonatal liver cells deminishes when there is a paucity of thyroxine. This is the main cause of hypothyroidism-induced jaundice.

400

What is Rhogam and when should it be given

(Extra points if you can name 3 sensitizing events)

Indication and implementation

  • Anti-D prophylaxis should be administered during the 28th week of gestation  and within 72 hours following the birth of an Rh-positive baby also following a sensitizing event.
  • The efficacy of anti-D prophylaxis relies on antibody-mediated immunosuppression. 
  • Further indications in Rh negativity
    • Following a miscarriage, ectopic pregnancy, or termination of pregnancy
    • Bleeding during pregnancy
    • Following invasive procedures (e.g., amniocentesis, chorionic villus sampling) 

SENSITISING EVENTS 

 Antepartum hemorrhage 

 Invasive diagnostic procedures e.g. amniocentesis, chorionic villus sampling 

 Other intrauterine procedures e.g. those carried out in fetal medicine unit (insertion of shunts) 

 External Cephalic Version 

 Intrauterine Death 

 Abdominal trauma

https://www.nice.org.uk/guidance/dg25/resources/clinical-guideline-rhesus-rhd-negative-antenatal-management-bristol-university-hospital-pdf-4368966308 


400

Complications of a Splenectomy 

Extra points for explaining the pathophys behind splectomy and increased susceptability to encapsulated bacteria infections

infection

bleeding

venous thromboembolism


Bonus-

Splenectomy → ↓ IgM production → ↓ complement activation → ↓ C3b opsonization → ↓ clearance of opsonized bacteria → ↑ susceptibility to infection by encapsulated bacteria. 

400

Outline the conditions associated with liver edges that are
Knobbly
Smooth
Pulsatile
Tender
Bruit

Smooth - venous congestion, fatty infiltration
Knobbly - metastases, cysts
Pulsatile - TR
Tender - hepatitis, RHF (capsular pain)
Bruit - HCC, AV malformation, TIPSS (transjugular intrahepatic portosystemic shunt)

400

Management of edema

0. History and Examination

1. Treat the Underlying Cause

  • Liver Cirrhosis: Address underlying liver disease with medications, lifestyle changes (e.g., alcohol cessation, weight loss), and potentially antiviral treatments for hepatitis.
  • Heart Failure: Optimize heart failure management with medications like diuretics, ACE inhibitors, and beta-blockers.
  • Malignancy: Treat underlying cancer with chemotherapy, radiation, or surgery as appropriate.

2. Dietary Modifications

  • Sodium Restriction: Limit sodium intake to less than 2 grams per day to reduce fluid retention.
  • Fluid Restriction: In severe cases or if hyponatremia is present, restrict fluid intake to 1.5 liters per day or less.

3. Diuretics

  • Spironolactone: Typically the first-line diuretic due to its potassium-sparing properties. Initial dose is usually 100 mg per day, which can be increased up to 400 mg per day if needed.
  • Furosemide: Often used in combination with spironolactone to enhance diuresis. Initial dose is 40 mg per day, which can be increased up to 160 mg per day.
  • Monitoring: Regularly monitor electrolytes, renal function, and weight to adjust diuretic doses and avoid complications such as hypokalemia or renal impairment.

4. Paracentesis

  • Therapeutic Paracentesis: Performed to relieve symptoms and discomfort from large-volume ascites. Up to 5 liters of fluid can be safely removed at one time.
  • Albumin Infusion: Administer albumin (6-8 grams per liter of ascitic fluid removed) during large-volume paracentesis (>5 liters) to prevent paracentesis-induced circulatory dysfunction.

5. Medications

  • Vasopressin Receptor Antagonists: Tolvaptan can be used in specific cases of hyponatremia associated with ascites.
  • Midodrine: A vasoconstrictor that can improve renal perfusion and is sometimes used in refractory ascites.

6. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

  • Indication: Considered for refractory ascites not responding to medical treatment.
  • Procedure: TIPS involves creating a channel within the liver to connect the portal vein to a hepatic vein, reducing portal hypertension.

7. Management of Complications

  • Spontaneous Bacterial Peritonitis (SBP): Prophylactic antibiotics (e.g., norfloxacin or ciprofloxacin) for patients with low protein ascites (<1.5 g/dL) or a history of SBP.
  • Hepatorenal Syndrome (HRS): Treat with vasoconstrictors (e.g., terlipressin) and albumin; consider liver transplantation for eligible patients.

8. Liver Transplantation

  • Indication: Considered for patients with end-stage liver disease and recurrent or refractory ascites.
400

All OR  NOTHING Billiary Atresia


  • Definition: obliteration or discontinuity of the extrahepatic biliary system, most commonly of the common bile duct
  • Epidemiology
    • Approx. 1:10,000–15,000 live births in the US
    • ♀ > ♂
  • Etiology
    • Exact etiology unknown, most likely an embryonal malformation or acquired lesion 
    • Approx. 10–35% of cases involve additional anatomical malformations (e.g., situs inversus, asplenia, polysplenia, cardiac anomalies)
  • Pathophysiology: discontinuity of the biliary system due to obliteration or fibrosis → obstruction of bile flow (cholestasis) → secondary biliary cirrhosis and portal hypertension
  • Clinical features
    • Jaundice
      • Prolonged neonatal jaundice (> 2 weeks)
      • Onset 2 weeks after birth is possible.
    • Acholic stools, dark urine
    • Hepatomegaly
  • Diagnosis
    • Laboratory analysis
      • Conjugated hyperbilirubinemia 
      • ↑ Aminotransferases and alkaline phosphatase
      • ↑ GGT
    • Ultrasonography
      • Absence of the gallbladder
      • No dilatation of the biliary tree
    • Liver biopsy
      • Active inflammation with bile duct degeneration and fibrosis 
      • Bile duct proliferation
      • Portal stromal edema
    • Hepatobiliary scintiscanning (HBSS): failed excretion of the tracer into the bowel
    • Intraoperative cholangiography to confirm diagnosis 
  • Treatment
    • Kasai procedure (hepatoportoenterostomy): a connection is created between the liver and the small intestine to allow for bile drainage.
    • In cases of liver cirrhosis: liver transplantation (primary reason for liver transplantation in children)
  • Complications
    • If undetected
      • Early biliary liver cirrhosis (at approx. 9 weeks of age)
      • Children may die within the first 2 years of life
    • Postoperative
      • Cholangitis in 50% of cases
      • Portal hypertension in > 60% of cases
500

What is Kernicterus and Presentation

An irreversible neurological syndrome that occurs in inadequately treated neonates with high levels of serum bilirubin (> 25 mg/dL) as a result of deposition of unconjugated bilirubin in the basal ganglia and/or brain stem nuclei. Long-term sequelae include hearing impairment, movement disorders (athetosis), intellectual disability, and dental enamel hypoplasia.  


  • Clinical features
    • Cerebral paresis, hearing impairment, vertical gaze palsy
    • Movement disorder (choreoathetosis)
    • Apparent intellectual and developmental disabilities 
    • Dental enamel hypoplasia
500

Indications for a Splenectomy


(why do scd patients develop functional asplenia )

Indications for splenectomy – Severe disease – Low Hgb with frequent need for transfusions – Aplastic crises – Poor growth – End-organ damage—cardiomegaly • Partial splenectomy can improve transfusiondependent children with severe case, while theoretically preserving some splenic function and protection against sepsis


functional Asplenia can develop as a complication of sickle cell disease as a result of repeated infarction secondary to vasoocclusion from sickle cell buildup.

500

Causes of hepatosplenomegaly

Bonus state what joint pathology can lead to hepatomegaly

Infection: EBV, Hepatitis, Malaria, HIV
Hematological: lymphoma, leukemia, myelofibrosis, beta thalassemia, G6PD deficiency
Infiltrative: sarcoidosis, amyloidosis
Storage disorders: mucopolysaccharidosis,
Congenital infection: rubella, syphilis
Syndromes: Wiskott-Aldrich Syndrome

500

What is Dialalysis

What are the types, indications and complications

Definition

Types-

  • Peritoneal dialysis
  • Hemodialysis or hemofiltration

Indications-“A.E.I.O.U.” -Acidosis, Electrolyte abnormalities (hyperkalemia), Ingestion (of poisons), Overload (fluid), Uremic symptoms 


Complications

Complications of peritoneal dialysis 8

  • Metabolic disturbances: weight gain, hyperglycemia 
  • Infections
    • Exit site and catheter tunnel infections
    • Peritoneal dialysis-associated peritonitis
  • Protein loss: hypoalbuminemia  [25]
  • Abdominal hernias: umbilical and inguinal hernias are most common [26]
  • Leakage of dialysate
  • Pleural effusion (rare)

Complications of hemodialysis 

Vascular access complications 

  • Loss of access due to thrombosis or stenosis
  • Infections e.g., skin and soft tissue infection, central line-associated bloodstream infection
  • Local aneurysm
  • AV access steal syndrome: painful ischemia of the hand secondary to the AV fistula or graft shunting blood away from the distal limb
  • Dialysis vascular access hemorrhage

Cardiovascular complications 

  • Hypotension  
  • Heart failure 

Increased bleeding risk

  • Caused by platelet dysfunction due to CKD and/or platelet contact with the dialysis membrane 
  • Avoid systemic anticoagulation solely to maintain or improve hemodialysis catheter patency.  

Dialysis disequilibrium syndrome

  • Definition: the development of acute cerebral edema secondary to the rapid extraction of osmotically active substances (e.g., urea, NaCl) from the blood 
  • Risk factors 
    • First dialysis sessions
    • Extremely elevated BUN
    • Metabolic acidosis
    • Preexisting neurological abnormalities
    • Hyperglycemia or hypernatremia
  • Prevention 
    • Use hemofiltration over hemodialysis in patients with risk factors.
    • If hemodialysis is performed, provide regular, slow dialysis. 
    • Consider adjusting the dialysate to mitigate osmotic shifts.  
  • Management: Monitor patients for symptoms of cerebral edema and initiate management of raised ICP if present. [17]

Other complications [2][7]

  • Acquired cystic kidney disease  [19]
  • Cramps
  • Electrolyte abnormalities, e.g., hypophosphatemia
  • Dialysis-related amyloidosis, which can cause carpal tunnel syndrome  [20][21]
  • Allergic reaction to the equipment or dialysate [3]
500

Go for gold Alagille syndrome

Alagille syndrome


  • Description: a genetic condition that is characterized by intrahepatic biliary duct aplasia or hypoplasia
  • Epidemiology: Approx. 1:30,000–45,000 live births in the US
  • Etiology
    • Autosomal-dominant inheritance
    • Mutation in the JAG1 gene on chromosome 20 in 90% of patients
  • Clinical features
    • Hepatic manifestations
      • Cholestasis
      • Jaundice
      • Pruritus
      • Cirrhosis
    • Facial dysmorphism
      • Triangular face
      • Deep set eyes
      • Broad nasal bridge
    • Congenital heart defects (e.g., peripheral pulmonary stenosis)
    • Butterfly vertebrae
    • Posterior embryotoxon
    • Renal dysplasia
  • Diagnosis
    • Laboratory findings
      • Conjugated hyperbilirubinemia
      • ↑ Serum aminotransferases
      • ↑ γ-GT
    • Liver biopsy: decreased number of interlobular bile ducts
    • Confirmation via genetic testing: detection of JAG1 gene mutation
  • Treatment
    • Depends on the affected organ systems
    • Conservative management of cholestasis and pruritus (e.g., ursodeoxycholic acid, cholestyramine)
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