Published on Mar 22, 2016
HARRISON's Secrets
5 high yielding topics to boost you PG entrance exam preparation
  1. Liver transplant
  2. Lithium induced nephrogenic DI
  3. Refeeding syndrome
  4. Mitochondrial DNA
  5. Stemcells

1) Liver transplant

  • It is an orthotopic transplantation, in which the native organ is removed and the donor organ is inserted in the same anatomic location. It was done 1st by Thomas Starzl, England in 1963. ). The first report of successful Living donor LT was by Dr. Christoph Broelsch in November 1989
  • Cold ischemic time-ideally is less than 12 hours.
  • Perfusion fluid- use of University of Wisconsin (UW) solution, rich in lactobionate and raffinose
  • Hepatitis C, is the most frequent indication for liver transplantation in adults. (AIPG-2010***) and in children ,it is biliary atresia
  • Model for end-stage liver disease (MELD) (TN-2011***)- it is the score which is currently considered for patients awaiting liver transplant. It has 3 variables-bilirubin, sr. Creatinine and prothrombin time
  • For children <18 years of age, the Pediatric End-Stage Liver Disease (PELD) scale is used. This scale is based on albumin, bilirubin, INR, growth failure, and age.
  • Living donor liver transplantation for pediatric recipients involves removal of approximately 20% of the liver (Couinaud segments 2 and 3*In amyloidosis ATTR type - transthyretin [AIIMS N0V - 2007***] is the primary protein component and this presents with orthostatic hypotensison. Treatment of familial cases with liver transplantation are tried.
  • Liver Transplantation- OLTX is done for patients with a single lesion 5 cm or three or fewer nodules, each 3 cm (Milan criteria).This resulted in excellent tumor-free survival (70% at 5 years).
  • Crigler-Najjar type I - complete absence of bilirubin UDPGT activity- the only effective treatment is orthotopic liver transplantation.
  • The vanishing bile duct syndrome and adult bile ductopenia - histologic picture is similar to that found in primary biliary cirrhosis. It is seen in chronic rejection after liver transplantation, in those who develop graft-versus-host disease after bone marrow transplantation, sarcoidosis, chlorpromazine.
  • Child-Pugh class B-indicates need for liver transplant
  • Paracetomol toxicity- Lactate levels >3. 5 mmol / L might need liver replacement.
  • Among children listed as candidates for liver transplantation, valproate is the most common antiepileptic drug implicated.(In children the commonest indication is biliary atresia)

2) Lithium induced nephrogenic DI

Lithium causes NDI by multiple mechanisms, including direct inhibition of renal glycogen synthase kinase-3 (GSK3), GSK3 is required for the response of principal cells to AVP.
The entry of lithium through the amiloride-sensitive Na+ channel ENaC is required for the effect of the drug on principal cells; thus, combined therapy with lithium and amiloride can stop lithium-associated NDI.


3) Refeeding syndrome

In the early stages of treatment, severely malnourished patients may develop a "refeeding syndrome" characterized by hypophosphatemia, hypomagnesemia, and cardiovascular instability.

4) Mitochondrial DNA

  • Mitochondria are cytoplasmic organelles whose major function is - oxidative phosphorylation in aerobic conditions by the respiratory electron transport chain (ETC) multiprotein enzyme complexes I–V and the two electron carriers, coenzyme Q (CoQ) and cytochrome c. Complex II, CoQ, and cytochrome c are encoded by nuclear DNA. In contrast, complexes I, III, IV, and V contain at least some subunits encoded by mtDNA
  • mtDNA molecules do not undergo recombination.
  • Mothers transmit their mtDNA to both their sons and their daughters
  • "Threshold" effect in which the actual expression of disease depends on the relative percentage of mitochondria whose function is disrupted by mtDNA mutations.
  • The most striking overall characteristic of mitochondrial genetic disease is the phenotypic heterogeneity associated with mtDNA mutations.
  • Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) is the most common mtDNA disease, consisting of a progressive encephalomyopathy characterized by repeated strokelike events involving mainly posterior cerebral areas


5) Stem cells

  • The term potency is used to indicate a cell's ability to differentiate into specialized cell types. Cultured stem cells are grouped according to their potency.
  • Potency- The hierarchy of stem cells are given below.Totipotency> Pluripotent> Multipotent cells> Oligopotent cells> Unipotent cells> Terminally differentiated cells.
  • Three genes,namely Pou5f1 (Oct3/4), Nanog, and Sox2 are the key gene regulatory pathways of self-renewal
  • Umbilical Cord Stem Cells are associated with less graft-versus-host disease.
  • Hematopoietic stem cells express the following cell surface molecules - CD34, Thy-1 (CD90), c-Kit receptor (CD117), CD133, CD164, and c-Mpl (CD110, also known as the thrombopoietin receptor).