Abdo Paces Flashcards
Causes of enlarged kidneys
ADPKD
Recessive form of PKD
Von Hippel Lindau
Tuberous Sclerosis
Hydronephrosis
Renal cell carcinoma (5%)
Genetics of PKD
Autosomal dominant:
PKD1: chromosome 16 in 80%- mean age to ESKD = 54
PKD2: chromosome 4 in 15% - mean age to ESKD = 74
Autosomal recessive:
Chromosome 6 - ESKD in early childhood
Clinical presentation on PKD
Abdominal mass or pain
Hypertension
UTI
Renal calculus
Haematuria
Intracranial bleed
Diagnostic criteria for ADPKD
In a patient known to be at 50% risk because of FHx, dx is suggested by:
- 2 cysts, either unilateral or bilateral at <30 yrs
- 2 cysts in each kidney in patients aged 30-59yrs
- 4 cysts in each kidney in patients >60yrs
- dx supported by hepatic or pancreatic cysts
In sporadic cases:
- bilateral renal enlargement and cysts, or the presence of multiple bilateral renal and hepatic cysts
- no manifestations suggesting an alternative renal cystic disease
Management of PKD
- management of cardiovascular risk factors
-BP control and RAAS blockade - tolvaptan (ADH receptor antagonist) limits cyst development
- may require nephrectomy to remove problematic cysts and reduce mass effects
- renal transplant and dialysis
Extra renal manifestations of PKD
- hypertension
- liver cysts (70%)
- pancreatic cysts (10%)
- berry aneurysms (5%)
- diverticular disease
- mitral valve prolapse
- aortic incompetence
- hepatic fibrosis
Pathophysiology of PBC
Autoimmune condition
Progressive inflammation and destruction of small intrahepatic ducts.
Antimitochondrial antibodies (AMA) is hallmark feature
Strongly associated with RA, sjorgens, CREST
Presentation of PBC
Incidental finding of raised ALP
Pruritus
Cholestatic jaundice
Diarrhoea
Lethargy
Xanthelasmata
Skin pigmentation
Clubbing
Hepatosplenomegaly
GI bleed
Osteoporosis
Diagnosis of PBC
AMA antibodies present in 95% of cases
Raised ALP
Raised IgM
May require liver biopsy for confirmation
Management of PBC
Cholestyramine for pruritis
Ursodeoxycholic acid
Obeyicholic acid either as mono therapy or combination with urso if not tolerated or response (reduces circulating bile acid)
Liver transplant
Complications of PBC
Hepatic cancer
Cirrhosis
Liver failure
Osteoporosis
Vitamin deficiency
Causes of hepatomegaly
Cirrhosis
Carcinoma
Congestive cardiac failure
Hepatitis B or C
PBC, PSC, AIH
Amyloid
Myeloproliferative disorder
Causes of cirrhosis
Alcohol
NAFLD
Hepatitis C and B
Autoimmune hepatitis
PBC
PSC
Wilson’s
Haemachromatosis
a1 antitripsin disease
HHT
Medications
Liver screen bloods
Autoimmune antibodies (ANA, AMA, SMA, LKM)
Immunoglobulins
Hepatitis b and c serology
Ferritin
Caeruloplasmin
a1 antitrypsin
AFP
Presenting a chronic liver disease patient
- Peripheral stigmata of liver disease
- Hepatomegaly
- Evidence of portal hypertension
- Evidence of decompensation
- Evidence of cause of liver disease
Classification of cirrhosis
Bilirubin, albumin, INR, ascites, encephalopathy
A= 5-6
B= 7-9
C= 10-15
Causes of palmer erythema
Cirrhosis
Hyperthyroidism
RA
Pregnancy
Polycythaemia
Causes of gynaecomastia
Puberty, old age
Kleinfelters syndrome
Cirrhosis
Drugs - spironolactone or digoxin
Testicular tumour/orchidectomy
Hyper/hypothyroidism
Addisons
Autoantibodies in PSC
ANA
anti- smooth muscle may be positive
Autoantibodies in autoimmune hepatitis
Anti smooth muscle
Anti LKM1
ANA
Causes of chronic renal failure
Diabetic nephropathy (34%)
Hypertension (29%)
Glomerulonephritis (14%)
PKD (14%)
Chronic pyelonephritis (10%)
Obstructive/reflux nephropathy
Advantages of transplant over continued dialysis
Improved quality of life
Increase patient survival rate
Cost effective in the long term
Renal diseases where there are a high risk of reoccurrence in transplanted kidney
Focal segmental glomerular sclerosis
Amyloidosiss
IgA nephropathy
HUS
Technical considerations for renal transplant
Atheromatous iliac vessels
Bladder dysfunction
Bleeding or infection on PKD cysts
Large and bulky kidneys
Uncontrolled hypertension
Renal calculi
Persistent anti- glomerular antibodies
Methods of transplant rejection
Hyper acute
- due to presence of recipient antibodies against the donor kidney
- requires removal of transplant kidney
Acute cell mediated rejection
- mononuclear cell infiltration occurs in the interstitial and subsequently in vessel walls
- treated with high dose steroids
Acute antibody mediated rejection
- at least 3/4 of graft dysfunction, histological evidence of tissue injury, positive staining for C4d, presence of donor specific antibodies
- poor prognosis, treated with plasmapheresis and IVIg
Chronic rejection
Kidney donor work up
-Cross match and screening of transmissible disease
- MRA and isotope renography
MOA and side effects of ciclosporin
Calcineurin inhibitor
Inhibits production of IL-2 and TNF-a by binding to ciclophilin protein and inhibiting calcineurin
SE: nephrotoxic, hyperkalaemia, hypomagnesaemia, gingival hypertrophy, hyperlipidaemia, glucose intolerance, hypertension
MOA and side effects of tacrolimus
Calcineurin inhibitor
Inhibits production of IL-2 by helper T cells, by binding Calcineurin to tacrolimus binding protein
SE: nephrotoxicity, neurotoxicity ( tremor), glucose intolerance, prolonged QT
MOA and SE of mycophenolate mofetil
A prodrug. The active compound is mycophenolic acid which inhibits the enzyme required for guanosine synthesis which results in impaired b and T cell proliferation.
SE: nausea, diarrhoea, leukopenia, anaemia, thrombocytopenia
MOA and side effects of azathioprine
Anti-metabolite to inhibit DNA and RNA synthesis
SE: leukopenia, thrombocytopenia, GI disturbance, cholestasis, alopecia
MOA and SE of steroids
Reduce IL-3, IL-6 and TNF-a production and inhibit T cell activation.
SE: glucose intolerance, oseoporosis, AVN, cataracts, cushiongoid appearance, infections, poor wound healing
MOA and SE of sirolimus
Inhibition of TOR (a regulatory kinase)
SE: hyperkalaemia, hypomagnesaemia, hyperlipidaemia, leukopenia, anaemia, impaired wound healing, joint pain
Complications of immunosuppression
- New onset diabetes after transplantation
- Hypertension
- Hyperlipidaemia
- SCC of the skin
- malignancy related to viral infection eg. HPV and cervical cancer, lymphoma and EBV, or Kaposi sarcoma and HHV-8
- CMV due to reactivation of endogenous disease or transmission from a donor
- BK infection
Prognostic factors of renal transplant
- primary diagnosis
- previous graft failure
- episodes of rejection
- kidney total ischaemic time
- donor factors eg. Age
CI to renal transplant
Active malignancy ( must be cancer free for 2 years)
Active infection
Advanced atheromatous disease is a relative contraindication
Calculating SAAG
Serum albumin - ascitic fluid albumin
Causes of increased SAAG
Cirrhosis
Alcoholic hepatitis
Schistosomiasis
Fulminant hepatic failure
Budd Chiari
Portal vein obstruction
Cardiac disease
SBP
Causes of normal or low SAAG
Nephrotic syndrome
Protein losing enteropathy
Peritoneal carcinomatosis
Tuberculous peritonitis
Pancreatic duct leak
Biliary ascites
Treatment of ascites
- fluid restriction
- low salt intake
- diuretic therapy
- paracentesis
- prophylactic abx
Indications for dialysis in CKD
Uraemic symptoms
Uncontrollable fluid overload
EGFR of 5-7
Indications for dialysis in AKI
Severe metabolic acidosis pH <7.1
Hyperkalaemia refractory to treatment
Refractory fluid overload
Signs of uraemia
Certain toxins
Complications of peritoneal dialysis
Bacterial peritonitis
Ultrafiltration failure
Encapsulating peritoneal sclerosis
Hernias
Fluid leak, eg through diaphragm causing pleural effusion
Malnutrition
Complications of haemodialysis
Hypotension
Infection, at access point or bacteraemia
Venous stenosis or occlusion
Air embolus
Anaphylactic reaction to sterilising agent
Long term complications of dialysis
Vascular disease
Cardiac valve calcification - particularly aortic
Dialysis related amyloid due to a build up of beta2 microglobulin
Pseudogout and gout
Causes of splenomegaly
- Infiltration
- lymphoma, amyloidosis, sarcoidosis, Gaucher’s disease, thyrotoxicosis - Increased function
- spherocytosis, thalassaemia, sickle cell anaemia, infections (chronic malaria, visceral leishmaniasis, glandular fever, brucellosis, RA with feltys, SLE, sarcoidosis - Abnormal blood flow
- cirrhosis with portal hypertension, hepatic or portal vein obstruction
Causes of massive splenomegaly
CML
Myelofibrosis
Gauchers storage disease
Chronic malaria
Kala- azar (visceral leishmaniasis)
Causes of moderate splenomegaly
Myelo/lymphoproliferative disorders
Infiltration eg. Amyloidosis
Causes of mild splenomegaly
Myelo/lymphoproliferative disorders
Portal hypertension
Infections eg. EBV, IE, infective hepatitis
Haemolytic anaemia
Investigations in patients with splenomegaly
US abdo
FBC + film
CT CAP
Bone marrow aspirate and trephine
Lymph node biopsy
Thick and thin films x 3 for malaria
Viral serology
Indications for splenectomy
Rupture (trauma)
Haematological (ITP or hereditary spherocytosis)
Splenectomy work up
Vaccination (ideally 2 weeks prior to protect against encapsulated bacteria)
- pneumococcus
- meningococcus
- haemophilus influenza
Prophylactic penicillin life long
Medic alert bracelet
Reasons for liver transplant
Cirrhosis
- alcohol, NAFLD, Haemachromatosis, Wilson’s
Acute hepatic failure
- hepatitis A and B, paracetamol overdose
Hepatocellular carcinoma
What scoring system is used for deciding to list chronic liver disease patients for transplant
Model for End Stage Liver Disease (MELD)
Comprised of INR, creatinine, bilirubin, sodium
Score > or = 49
Complications of liver transplant
Initially:
- haemorrhage, graft failure, infection, vascular and biliary complications, rejection
Delayed complications:
- immunosuppression side effects, disease relapse, chronic graft rejection
Clinical signs of haemochromatosis
Increased skin pigmentation (slate grey colour)
Stigmata of chronic liver disease
Hepatomegaly
Venesection scars
Liver biopsy scar
Swelling and squaring off of MCP joints
Joint replacement scars
CCF
Evidence of diabetes monitoring (Bronze diabetes)
Hypogonadism and testicular atrophy
Inheritance of haemochromatosis
Autosomal recessive on chromosome 6
Variable penetrance
HFE gene mutation: regulator of gut iron absorption
Males affected earlier then females due to menstrual iron losses
How May Haemachromatosis present
Fatigue
Arthritis
Chronic liver disease
Screening
Investigations for Haemachromatosis
Dx:
Increased serum ferritin
Increased transferrin saturation
Liver biopsy used to assess severity of cirrhosis
Genotyping
Additional:
BM/ HbA1c
ECG, CXR, Echo
Us liver, afp
Joint X-rays: chondrocalcinosos
Treatment of haemochromatosis
Regular venesection (1unit/week) until ferritin 20-30mg/L and transferritin saturation <50%
Then maintenance venesection 1 unit 3-4 times/ year based on ferritin and transferritin levels
Avoid alcohol
Surveillance for HCC
Screening for haemochromatosis
1st degree relative >20 yrs old:
Ferritin > 300 in men and >200 in women
Transferrin saturation > 50% in males and > 40% in females
If positive:
genotyping
Prognosis of haemochromatosis
200x increased risk of HCC if cirrhotic
Reduced life expectancy if cirrhotic
Normal life expectancy without cirrhosis + effective treatment
Pathogenesis of Haemachromatosis
Mutation in the HFE gene which causes increased intestinal iron absorption, leading to iron deposition in joints, liver, heart, pancreas, pituitary, adrenals and skin
Pathophysiology of hereditary spherocytosis
An inherited defect in the structural proteins of red blood cell membranes (usually dominant inheritance). Mutation in 1 of 5 genes. Abnormalities result in changes in red cell shape due to defects in skeletal proteins (alpha spectrin, beta spectrin, ankyrin, band 3 protein and protein 4.2).
These red cells are more fragile and so go through haemolysis predominantly in the spleen
Clinical presentation of hereditary spherocytosis
Pallor, jaundice, splenomegaly, fatigue, RUQ pain (gall stones)
Inv/diagnosis in suspected hereditary spherocytosis
Low Hb, increased mean corpuscular Hb concentration, MCV low
Reticulocyte count elevated
Blood smear showing spherocytes
Elevated unconjugated bilirubin
DAT -ve
EMA binding or Osmotic fragility test
Management of hereditary spherocytosis
Folic acid supplementation
Splenectomy +/- cholecystectomy
Pre op vaccination regime + post op prophylactic abx
Complications of hereditary spherocytosis
Aplastic crisis usually secondary to infection
Anaemia
Gall stones
Bone marrow expansion
Extramedullary haematopoeisis
Post splenectomy sepsis
Post splenectomy thrombosis
Aetiology of coeliac disease
Gluten peptides are found in barley, wheat and rye.
There is an increased immunological response to ingested gluten.
Predisposing factors include: association to HLA antigens, presence of HLA-DQ2 in 95%, the rest are DQ8, other autoimmune conditions.
Pathophysiology of coeliac disease
Gluten peptides are resistant to human proteases allowing them to persist in the small intestinal lumen. These peptides trigger immune activation in the intestinal submucosa mediated by T helper cells.
Epithelium of small intestine is damaged causing loss of brush border, villous atrophy, crypt hyperplasia.
Associated conditions with coeliac disease
Dermatitis herpetiformis
Down syndrome
Selective immunoglobulin A deficiency
Auto immune conditions
Diagnosis and inv of coeliac disease
FBC, iron studies, b12, folate, calcium
IgA tTg levels
EMA
Small intestinal biopsy showing intraepithelial lymphocytes, villous atrophy, crypt hyperplasia
Where would you expect to palpate combined pancreatic and kidney transplant?
Pancreas: right iliac fossa
Kidney: left illiac fossa
Prognosis of SPK transplantation vs. Isolated renal transplant
10 year prognosis similar
>10 years spk has greater survival
Benefits of pancreatic transplant
Improved quality of life
Improved glycaemic control
Does not reverse established CVD but does slow progression
Improved neuropathy
Improved nephropathy
The effects on retinopathy are unclear
Pathophysiology of alcohol dependency
Long term alcohol consumption down-regulates inhibitory neuronal GABA receptors, up regulates excitatory glutamate receptors and increases norepinephrine activity.
Cessation of alcohol leaves the excitatory state unopposed.
Pathogenesis of alcohol liver disease
Alcohol metabolism requires alcohol dehydrogenase, this process reduces NAD to NADH. Excessive NADH increases fatty acid synthesis, promoting fatty infiltration.
Pathogenesis of alcoholic hepatitis
Acetaldehyde binds to macromolecules in hepatocytes eg. Enzymes and proteins. The immune system detects these complexes and neutrophil infiltration occurs. Hepatocyte necrosis and inflammation occurs.
Pathogenesis of cirrhosis
Alcohol directly affects stellate cells which transform into collagen- producing myofibroblast cells. There is loss of normal hepatic architecture with modular regeneration and fibrosis.
Causes of chronic pancreatitis
Alcohol
Cystic fibrosis
Smoking
Hypercalcaemia/hyperlipidaemia
Autoimmune disease
Drugs eg. Azathioprine
Clinical presentation of chronic pancreatitis
Malabsorption and steatorrhoea
Abdomen pain radiating to the back
Pain may be relieved by leaving forward
DM
Erythema ab igne
Clinical presentation of acute pancreatitis
Severe epigastric pain radiating to back
Worse after meals, improved on leaning forward
N&V
Tachycardia/hypotension/oliguria
Cullens sign
Grey-turners sign
Investigation of acute pancreatitis
AXR: sentinel loop of adynamic bowel adjacent to pancreas
Raised amylase and lipase
CT
Investigating chronic pancreatitis
Pancreatic calcification on AXR or CT
ERCP: irregular dilatation and stricturing of the pancreatic ducts
MRCP
EUS
Faecal elastase
Oral glucose tolerance test
Management of chronic pancreatitis
Abstain from alcohol and smoking
Creon + PPI
Dietitian assessment
Analgesia
Diabetes monitoring
Vit D replacement
Kings college criteria for transplant in paracetamol overdose
pH < 7.3
Or all of the following:
- PT > 100
- creatinine > 300
- grade 3 or 4 encephalopathy
Kings college criteria for liver transplant in acute liver failure
PT > 100
Or any 3 of the following;
Age <10 or > 40
Bili > 300
Coag- INR > 3.5
Duration (jaundice to HE > 7 days)
Etiology- absence of hep A or B or presence of a drug reaction
What is the cause of Wilson’s disease?
Autosomal recessive defect in ATP7B on chromosome 13, resulting in reduced excretion of copper into the bile and subsequent accumulation in other organs including the liver and brain
Investigations for Wilson’s disease
Low caeruloplasmin levels
High urinary copper levels
How is Wilson’s managed
Avoidance of high copper containing foods (shellfish, avocados)
Alcohol cessation
Copper chelation with penicillamine and zinc acetate
How can Wilson’s present
Acute or chronic liver failure
Haemolysis
Neurological involvement inc. movement disorders
Psychiatric manifestations
Cardiomyopathy
Fanconi’s syndrome
What are the commonest causes of HCC
CLD particularly hepatitis b and c, alcoholism, hereditary haemochromatosis and PBC. In some countries there is a link with aflatoxins.
What primary sites metastasise to the liver?
Stomach, pancreas, colon, lung, breast, ovarian, melanoma
Evidence of pancreatic exocrine insufficiency
Fatty stools
Weight loss
Vit D deficiency
Hypomagnesia
Low faecal elastase
