Station 1: Abdominal

2

Hints for the Abdominal Station

Abdominal Case with a Normal Abdomen

Chronic Liver Disease

Generalised Lymphadenopathy

Hepatosplenomegaly

Multiple Abdominal Scars

Palpable Kidneys

Renal Replacement Therapy

Splenomegaly

Abdominal Station Summary

HINTS FOR THE ABDOMINAL STATION

Read the candidate information carefully and look closely from the end of the bed for any signs that may help guide you to the specific examination; renal/ haematology/liver/general abdominal.

For a renal examination, look for evidence of renal replacement therapy (RRT). Always check for arteriovenous (AV) fistulae along the arms and look for fresh venepuncture marks at a fistula site. Also look for evidence of previous internal jugular vein lines or scars from peritoneal dialysis (PD) catheter insertions. Don’ t miss nephrectomy and pelvic transplant scars.

For a liver exam, ensure that you comment on the presence of finger clubbing, leuconychia, palmar erythema, Dupuytren’ s contractures and tattoos if present.

Look in the oral cavity; gum hypertrophy in ciclosporin toxicity, poor dentition in chronic liver disease and glossitis in anaemia.

If you find evidence of any cervical lymphadenopathy, always go on to check for axillary and inguinal lymphadenopathy.

Ensure that the patient is adequately exposed and that they are lying as flat as possible prior to palpating the abdomen.

Always make constant eye contact with the patient when palpating their abdomen to ensure that they are not in any discomfort. Apologise if you do cause any discomfort to the patient.

Do not panic if you cannot elicit any abnormal findings; the patient may have a normal abdomen. In this case, look for peripheral signs which may help guide you towards a diagnosis.

If you elicit any hepatomegaly or splenomegaly, always try to comment on the size of the organomegaly. In a case of splenomegaly, this may aid you with your differential diagnosis.

Look for evidence of peripheral oedema.

ABDOMINAL CASE WITH A NORMAL ABDOMEN

Please examine this patient’ s abdomen.

FINDINGS

 

General: Cachexia

Peripheral: Oral/perioral telangiectasia, buccal pigmentation, hypertension, facial flushing, lymphadenopathy, cushingoid features, signs of RRT

Abdomen: No abnormality

If you finish your examination and have no positive findings, it is likely that you are in one of the three following scenarios:

1.You have been given a patient with a normal abdomen.

2.You may have missed a peripheral sign that points to a diagnosis such as hereditary haemorrhagic telangiectasia (HHT), Peutz– Jeghers syndrome, generalised lymphadenopathy, Cushing’ s syndrome, carcinoid syndrome or a patient with end-stage renal disease (ESRD) on RRT

3.You may have missed organomegaly.

PRESENTATION

This patient has oral telangiectasia and looks clinically anaemic. There is nothing abnormal to find in the abdomen. The diagnosis may be hereditary haemorrhagic telangiectasia. I would like to know this patient’ s full blood count (FBC) and ask if there is a family history of this disorder.

QUESTIONS

1.What is the mode of inheritance of Peutz– Jeghers syndrome?

Autosomal dominant, caused by mutations in the STK11 (also known as LKB1), which is a tumour suppressor gene

2.What are the manifestations of Peutz– Jeghers syndrome?

This condition is characterised by dark-coloured freckling from mucocutaneous lesions predominantly on the face (around lips and mouth), oral mucosa and peripheries. It also causes polyps within the gastrointestinal (GI) tract which may be complicated by bleeding, intestinal obstruction and chronic pain and have a high risk of malignancy during their lifetime (particularly breast, colorectal, pancreatic, stomach ovarian, lung and small bowel).

3.What is the mode of presentation of hereditary haemorrhagic telangiectasia?

Recurrent epistaxis in childhood with red spots on lips, tongue, fingertips ± family history.

It is also known as Osler– Weber– Rendu syndrome.

It is characterised by multiple telangiectasia.

The patient is at risk of haemorrhage from AV malformations, particularly pulmonary and cerebral.

4.What is the mode of inheritance of hereditary haemorrhagic telangiectasia?

It has an autosomal dominant mode of inheritance. More than 80% of cases are due to mutations in ENG or ACVRL1 genes. MADH4 gene mutations have also been reported.

KEY POINTS

If you are unable to elicit any positive ?ndings, you may have been given a ‘ normal abdomen’ as your case.

Ensure that you look carefully for the presence of any peripheral signs to help guide your diagnosis.

Do not make up any ?ndings.

CHRONIC LIVER DISEASE

Please examine this patient who has presented with abdominal swelling.

FINDINGS

General: Cachexia, poor dentition, muscle wasting, loss of body hair, gynaecomastia, testicular atrophy, tattoos, pedal oedema

Skin: Excoriation marks, purpura, spider naevi (most likely to be seen on the chest/ back)

Hands: Clubbing, palmar erythema, leuconychia, Dupuytren’ s contractures

Face: Icterus, parotid swelling, pallor

Abdomen: Caput medusae, ascites, hepatomegaly, hepatic bruit, splenomegaly, evidence of previous ascitic taps/drains

PRESENTATION

On examination, this patient has evidence of chronic liver disease. There is leuconychia and palmar erythema. The patient is icteric and there are excoriation marks. There is marked ascites with prominent superficial veins over the abdominal wall.

This is a common presentation, so be sure to look for an underlying cause. The most common cause is alcoholic liver disease (ALD).

CAUSES

ALD

Parotid swelling, cachexia, Dupuytren’ s contracture

Viral hepatitis

Tattoos, injection sites

Wilson’ s disease

Kayser– Fleischer rings, Parkinsonism, cognitive impairment, features of heart failure

Haemochromatosis

Slate-grey pigmentation, evidence of diabetes mellitus, features of heart failure, arthritis

Alpha-1 antitrypsin deficiency

Shortness of breath, hyperinflated chest, evidence of cor pulmonale, clubbing (bronchiectasis)

INVESTIGATIONS

Bloods

FBC, urea and electrolytes (U&Es), liver function tests (LFTs) including albumin, gamma-glutamyl transpeptidase (GGT), coagulation screen, hepatitis serology, caeruloplasmin, ferritin, autoantibodies (antimitochondrial antibody [AMA], anti– smooth muscle, anti– liver kidney microsomal [LKM], antinuclear antibody [ANA]), alpha-fetoprotein (AFP), thyroid function tests (TFTs), coeliac screen, alpha-1 antitrypsin levels, glucose

Ascitic fluid

Gram stain and cell count (> 250 white cells/mm3 is indicative of spontaneous bacterial peritonitis [SBP]), protein concentration, culture

Imaging

Ultrasound scan (USS): Check for hepato-/splenomegaly, confirm ascites

Doppler flow studies of the hepatic/portal vein: Rule out thrombosis

Computerised tomography (CT) abdomen (adds little if USS is normal)

MANAGEMENT

Dependent on the underlying cause

Alcohol

Alcohol avoidance, diuretics, vitamin B compound, thiamine, oesophagogastroduodenoscopy (OGD) to look for oesophageal varices

Hepatitis

Hepatitis C: Antiviral agents

Wilson’ s disease

Chelation: Penicillamine, trientine

Haemochromatosis

Venesection (to a ferritin level of below 50 µg/L)

Alpha-1 antitrypsin deficiency

Generally supportive; advise not to smoke. Alpha-1 antitrypsin may be an option.

All these patients should be considered for liver transplantation on an individual basis if severity dictates.

QUESTIONS

1.What are the signs of decompensated chronic liver disease?

Encephalopathy: Grade 1 (altered mood/behaviour) to grade 4 (coma)

Asterixis

Jaundice

Ascites

Hepatic fetor

Constructional apraxia: Unable to draw a five-pointed star

2.What are the reversible causes of hepatic encephalopathy?

Alcohol

Drugs

GI haemorrhage

Infection

Constipation

3.How is ascites investigated?

The protein level of the ascites is used to split the aetiology by transudative and exudative causes. However, the serum ascites-albumin gradient (SA-AG) is more accurate for diagnosis of the cause. SA-AG is calculated as ‘ serum albumin concentration minus ascites albumin concentration’ .

SA-AG ≥ 11 g/L

Cirrhosis, cardiac failure, nephrotic syndrome

SA-AG < 11 g/L

Malignancy, pancreatitis, tuberculosis

Further investigations are also helpful for diagnosis:

Neutrophil count and microscopy and culture for spontaneous bacterial peritonitis (neutrophil count > 250 cells/mm3 is diagnostic of SBP)

Amylase for pancreatitis

Cytology for malignancy

4.What are the possible indications for liver transplantation in an adult?

Acute causes

Paracetamol poisoning (acetaminophen poisoning)

Other drugs, e.g. isoniazid, phenytoin, sodium valproate

Acute hepatitis

Epstein– Barr virus (EBV) and cytomegalovirus (CMV)

Chronic causes

Alcoholic liver disease

Primary biliary cirrhosis

Primary sclerosing cholangitis

Chronic viral hepatitis

Wilson’ s disease

Budd– Chiari syndrome

Hepatic malignancy

KEY POINTS

Look out for examination findings which will guide you to the underlying diagnosis.

In chronic liver disease, many patients will have a shrunken cirrhotic liver rather than hepatomegaly.

Be able to grade the various stages of hepatic encephalopathy.

REFERENCE

Moore KP, Aithal GP. (2006) Guidelines on the management of ascites in cirrhosis. Gut 55: 1– 12.

GENERALISED LYMPHADENOPATHY

Please examine this patient’ s abdominal system.

FINDINGS

General: Evident lumps and bumps, purpura, pallor, cachexia

Peripheral: Lymphadenopathy (cervical, supraclavicular, axillary), arthritis, enlarged tonsils

Abdomen: Splenomegaly, hepatomegaly, inguinal lymph nodes

PRESENTATION

This patient has marked lymphadenopathy. There are palpable nodes in the cervical, axillary and inguinal regions. There are purpuric lesions present on both arms. This could be a lymphoproliferative disorder with thrombocytopenia.

A difficult case, this could be picked up when examining the neck or following palpation of an enlarged spleen (and possibly liver). If following examination of the abdomen you feel that the patient could have a lymphoproliferative disorder, do not be afraid to reexamine the neck and axillae for nodes.

INVESTIGATIONS

Diagnosis

Blood tests (FBC, lactate dehydrogenase [LDH], blood film, viral screen, autoimmune screen, LFTs), lymph node biopsy, bone marrow aspirate and trephine, chest X-ray and sputum for acid-fast bacilli

Staging

CT/positron emission tomography (PET), lumbar puncture

MANAGEMENT

Dependent on the cause.

The main objective of treatment of high-grade lymphoproliferative disease is to achieve a cure.

Long-term remission may be achieved in low-grade disease.

It is also important to manage symptoms accordingly.

QUESTIONS

1.What is the differential diagnosis of generalised lymphadenopathy?

Lymphoproliferative disease: Chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia, Hodgkin’ s and non-Hodgkin’ s lymphoma

Viral disease: Includes human immunodeficiency virus (HIV), EBV and CMV

Other infections: Includes tuberculosis, brucellosis and toxoplasmosis

Inflammatory disease: Sarcoidosis, rheumatoid arthritis, systemic lupus erythematosus (SLE)

2.How are Hodgkin’ s and non-Hodgkin’ s lymphoma differentiated pathologically?

Through the presence of Reed– Sternberg cells in Hodgkin’ s lymphoma. These are characteristic binucleate cells found on light microscopy of a biopsy.

3.What are ‘ B-symptoms’ and what are their significance?

These include weight loss (> 10% in 6 months), unexplained fever > 38.0° C and night sweats. B-symptoms are included in the Ann Arbor staging classification of non-Hodgkin’ s and Hodgkin’ s lymphoma and indicate a poorer prognosis.

4.Tell me about CLL.

This is due to a monoclonal proliferation of lymphocytes, usually B-cells.

It is most commonly suspected from a routine blood test, with a raised white cell count (lymphocytosis). It may also present with signs of bone marrow failure (fatigue, infections, bleeding) or constitutional symptoms (such as weight loss, fevers, fatigue and malaise).

Investigations may include a CT scan, lymph node biopsy and bone marrow biopsy. CLL is staged by the Binet system (Stage A: < 3 groups of enlarged lymph nodes, no anaemia or thrombocytopenia; Stage B: ≥ 3 groups of enlarged lymph nodes, no anaemia or thrombocytopenia; Stage C: anaemia and/or thrombocytopenia). Cytogenetic testing can give information on how the disease is likely to progress, and can therefore guide treatment.

Stage A disease can initially be managed with a watch and wait approach. More advanced disease requires earlier intervention with cytotoxic chemotherapy (such as fludarabine and cyclophosphamide) and monoclonal antibodies (such as rituximab, a CD20 antibody). B-cell receptor signalling pathway inhibitors such as ibrutinib and idelalisib are also now available. Rarely, a bone marrow transplant is carried out.

Complications of CLL include bone marrow failure, autoimmune haemolytic anaemia, recurrent chest infections and acute transformation (Richter’ s syndrome).

KEY POINTS

When examining a seemingly normal abdomen, do not forget to feel for inguinal lymph nodes.

Be able to give a wide differential for lymphadenopathy.

Remember that a haematological cause is not the only cause of lymphadenopathy.

REFERENCES

Binet JL, et al. (1981) A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48(1): 198– 206.

Woyach JA, Johnson AJ. (2015) Targeted therapies in CLL: Mechanisms of resistance and strategies for management. Blood 126(4): 471– 7.

HEPATOSPLENOMEGALY

Please examine this patient’ s abdominal system.

FINDINGS

General: Purpura, pallor, jaundice

Peripheral: Enlarged tonsils, lymphadenopathy (cervical, supraclavicular, axillary), features of chronic liver disease

Abdomen: Splenomegaly (note degree of enlargement), hepatomegaly, ascites, inguinal lymph nodes

PRESENTATION

This patient has 10 cm splenomegaly, with 4 cm hepatomegaly. There is no evident lymphadenopathy and no peripheral features of chronic liver disease. The most likely diagnosis is a myeloproliferative disorder.

A common case, the most likely causes are chronic liver disease and haematological malignancy; be sure to look for signs of both of these. After the enlarged liver and spleen have been palpated, reexamine for peripheral signs if necessary.

INVESTIGATIONS

If the diagnosis is chronic liver disease, investigate as necessary (see chronic liver disease case). Otherwise, consider the following tests:

Blood tests

FBC, LDH, blood film, viral screen, autoimmune screen, LFTs, renal function, serum and urine electrophoresis

Imaging

Abdominal ultrasound, CT/PET scan

Invasive

Lymph node biopsy, bone marrow aspirate and trephine, other biopsy site (e.g. renal biopsy for amyloidosis)

MANAGEMENT

Dependent on the cause

QUESTIONS

1.What is the differential diagnosis of hepatosplenomegaly?

Chronic liver disease with portal hypertension

Lymphoproliferative disease: Chronic lymphocytic leukaemia, Hodgkin’ s and non-Hodgkin’ s lymphoma (in acute lymphoblastic leukaemia the spleen is not usually greatly enlarged)

Myeloproliferative disease: Chronic myeloid leukaemia (CML) (and acute myeloid leukaemia), polycythaemia rubra vera (PRV), essential thrombocythaemia and myelofibrosis

Other haematological disease: Thalassaemia, sickle cell disease

Viral disease: Includes HIV, EBV, CMV and hepatitis B/C (may cause chronic liver disease)

Other infections: Includes malaria, brucellosis, toxoplasmosis and leptospirosis

Inflammatory disease: Sarcoidosis

Infiltrative disease: Glycogen storage disease, amyloidosis

2.What are the myeloproliferative disorders?

A group of conditions caused by abnormal myeloid stem cell proliferation in the bone marrow. They are generally distinguished from each other by the type of cell which is most affected:

Red blood cells: Polycythaemia rubra vera

White blood cells: Chronic myeloid leukaemia

Platelets: Essential thrombocythaemia

Fibroblasts: Myelofibrosis

3.How might a patient with CML present, and how would you diagnose this?

Chronic myeloid leukaemia is the uncontrolled growth of myeloid cells. Therefore, red cells, white cells and platelets can all be affected. It could present as a result of the effect on these cells (fatigue, infection, bleeding), or with constitutional symptoms, abdominal pain (splenomegaly) or by chance.

For diagnosis, blood tests (raised white cell count) are relevant, but cytogenetic testing of bone marrow is usually required. On such chromosome analysis, the Philadelphia chromosome (a translocation between chromosomes 9 and 22, resulting in oncogenic fusion of the BCR-ABL1 gene [a type of tyrosine kinase]) is present in 95% of cases of chronic myeloid leukaemia. This chromosomal translocation forms the basis of targeted treatment with tyrosine kinase inhibitors (such as imatinib).

4.Tell me about amyloidosis.

This is a multisystem disease that results from extracellular deposition of abnormal proteins.

There are two main types: amyloid L (AL) and amyloid A (AA).

AL results from abnormal light-chain production and most commonly occurs on its own, although it can also be seen alongside myeloma. Deposition can affect the heart (cardiomyopathy and heart failure), kidneys (renal failure), nerves (peripheral neuropathy), gut (malabsorption) and clotting function. It is mainly diagnosed on biopsy, although a serum amyloid P (SAP) scan is sometimes carried out. Treatment is similar to that for myeloma. The complications can also be treated (for example, with a renal transplant).

AA results from abnormal deposition of serum amyloid A (SAA) protein, which is an acute-phase protein. It occurs as a secondary process to chronic inflammatory disorders (such as rheumatoid arthritis and familial Mediterranean fever) and chronic infections. It most commonly affects the liver, spleen and kidneys. It is again diagnosed by biopsy. The condition often improves with treatment of the underlying inflammatory disorder.

KEY POINTS

Aim to decide between liver and haematological disease when giving a primary diagnosis.

Look for clues of these two groups throughout the examination.

Don’ t be afraid to re-examine for peripheral signs if necessary.

REFERENCE

Pinney JH, Hawkins PN. (2012) Amyloidosis. Ann Clin Biochem 49(Pt 3): 229– 41.

MULTIPLE ABDOMINAL SCARS

This patient has had an operation. Please examine their abdomen.

FINDINGS

General: Cachexia, cushingoid features

Peripheral: Oral ulceration, pallor, finger-prick marks (signs of glucose testing), gum hypertrophy and hypertension (side effects of ciclosporin)

Abdomen:

Multiple surgical scars (most commonly midline)

Stoma sites (past/current)

Evidence of previous PD catheter exit site or removal (see case on RRT) or repeated ascitic drainage

Mention that you would wish to perform a rectal examination

Comment on nutritional state

PRESENTATION

This patient has inflammatory bowel disease (IBD) as evidenced by cachexia, clinical anaemia and multiple scars on the abdomen suggesting fistulae, bowel obstruction or abscess drainage. A per rectal examination may be useful to look for fistulae and abscesses.

INVESTIGATIONS

Stool cultures × 3 (microscopy/culture/Clostridium difficile toxin [DCT]) (in acute presentations).

Bloods including FBC, C-reactive protein (CRP), LFTs (evidence of associated liver disease, e.g. autoimmune hepatitis primary biliary cirrhosis).

A faecal calprotectin test (evaluates bowel inflammation); a negative test rules out inflammatory bowel disease.

Abdominal X-ray to rule out toxic megacolon (in acute presentations).

Sigmoidoscopy/colonoscopy and biopsy (for histological confirmation).

Magnetic resonance imaging (MRI) enterocolysis (MRI of the small bowel) or bowel ultrasound (in expert hands) can be used if Crohn’ s is suspected and to detect small bowel strictures.

MANAGEMENT

Medical

Immunosuppression including steroids, 5-aminosalicylic acid (ASA), disease-modifying agents such as azathioprine/mercaptopurine/methotrexate and biological agents

Surgical

Indications include fistulae, strictures and failure to respond to medical therapy

Nutritional support and elemental and low-residue diets

Psychological support

QUESTIONS

1.What are the differences between ulcerative colitis (UC) and Crohn’ s disease?

Differences between Crohn’ s Disease and Ulcerative Colitis

 

Crohn’ s disease

Ulcerative colitis

Distribution

Patchy (‘ skip lesions’)

Continuous

Depth

Transmural

Superficial

Area involved

Whole gastrointestinal
tract with predilection for
terminal ileum and anus

Large bowel with
predilection for
rectum

Smoking

Higher risk

Lower risk

Fistulae and stenosis

Common

Rare

2.What are the extra-intestinal manifestations of inflammatory bowel disease?

Skin: Erythema nodusum, pyoderma gangrenosum, aphthous ulceration

Joints: Seronegative arthritides (mostly large-joint arthritis and sacroiliitis)

Eye: Uveitis, episcleritis/scleritis, conjunctivitis

Hepatobiliary: Primary sclerosing cholangitis (more likely in UC), cholangiocarcinoma

Renal: Oxalate stones

3.What screening tests should you consider before initiating biological therapies?

History and examination (looking specifically for features of tuberculosis)

Hepatitis serology

HIV test

Chest X-ray (CXR)

T-spot test (QuantiFERON® test is adequate if patient is not on steroids)

4.What biological agents are available for the treatment of IBD?

Ulcerative colitis

Infliximab and golimumab are recommended by the National Institute for Health and Care Excellence (NICE) for the treatment of moderate to severe active UC in adults who have had a poor response to conventional therapy (including steroids and mercaptopurine or azathioprine), or if they have been unable to tolerate or have contraindications to such therapy.

Crohn’ s disease

Infliximab and adalimumab are recommended by NICE for adults with severe active Crohn’ s disease who have not responded to conventional therapy, or who have been unable to tolerate or have contraindications to conventional therapy.

A novel agent called vedolizamab is now available for those who fail first-line treatment; this is for both UC and Crohn’ s disease.

KEY POINTS

Look for the extra-intestinal manifestations of in?ammatory bowel disease to help guide the underlying diagnosis.

Familiarise yourself with the key treatments available for the management of these conditions.

Be aware that midline scars may not just be a sign of IBD – see case on RRT, if there’ s a midline scar – do not miss a kidney– pancreas transplant.

REFERENCES

National Institute for Health and Care Excellence. (2012) Guidance CG152. Crohn’ s disease: Management. Available from https://www.nice.org.uk/guidance/cg152. Accessed 2 May 2016.

National Institute for Health and Care Excellence. (2013) Guidance CG 166. Ulcerative colitis: Management. Available from https://www.nice.org.uk/guidance/cg166/chapter/1-recommendations. Accessed 2 May 2016.

National Institute for Health and Care Excellence. (2015) Guidance TA329. Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy. Available from https://www.nice.org.uk/guidance/ta329/chapter/1-Guidance. Accessed 2 May 2016.

Parente F, et al. (2002) Bowel ultrasound in assessment of Crohn’ s disease and detection of related small bowel strictures: A prospective comparative study versus x ray and intraoperative findings. Gut 50(4): 490– 5.

PALPABLE KIDNEYS

This patient has presented with haematuria. Please examine their abdomen.

FINDINGS

General: Signs of anaemia, hypertension and renal replacement therapy

Arms: Arteriovenous fistulae/grafts

Face: Gum hypertrophy from immunosuppressants

Fundoscopy: Hypertensive retinopathy and evidence of Von Hippel– Lindau syndrome

Chest/neck: Scars from previous tunnelled dialysis catheters

Abdomen: Enlarged kidneys (bilateral flank masses), hepatomegaly (associated with autosomal dominant polycystic kidney disease [ADPKD]), renal transplant and nephrectomy scars

Legs: Oedema

PRESENTATION

The diagnosis is autosomal dominant polycystic kidney disease. On inspection, there is the appearance of fullness in the flanks. On palpation, there are bilateral bimanually ballotable masses in the flanks. It is possible to get above the masses, and each moves with respiration.

TIPS

Ensure that you comment on any evidence of renal replacement therapy, e.g. the presence of a tunnelled vascular catheter, a peritoneal dialysis catheter or an AV fistula in the arms. In addition, on abdominal examination you may note a J-shaped renal transplant scar in the iliac fossa and/or a subsequent midline scar from where the enlarged kidneys may have been removed.

INVESTIGATIONS

Urinalysis

Haematuria and proteinuria, signs of infection

Ultrasound abdomen

Gold standard investigation to assess renal size, cysts, obstruction, liver cysts

CT abdomen

To look for malignancy if clinically indicated

MRI

To assess renal size and volume (if indicated)

Echocardiogram

Examine for mitral valve prolapse (MVP), aortic disease and assess ventricular function

Cerebral angiogram

Evidence of berry aneurysms associated with ADPKD.

Only indicated if a first-degree relative with ADPKD had a subarachnoid haemorrhage/bleeding aneurysm. Routine scanning in all is not indicated.

Genetic testing

Autosomal dominant polycystic kidney disease (ADPKD 1 and 2)

MANAGEMENT

Counselling

Regular surveillance

Monitor renal function, treat hypertension and manage chronic kidney disease (CKD) and complications

Consider nephrectomy if appropriate

Vasopressin antagonists – tolvaptan – inhibits binding of vasopressin to V2 receptors, reducing cell proliferation, cyst formation and fluid excretion. NICE recommends this if PKD with CKD stage 2 or 3 at the start of treatment with evidence of rapidly progressive disease

Renal replacement therapy if required

Investigation of first-degree relatives

QUESTIONS

1.What is the genetic basis of polycystic kidney disease?

ADPKD

Affects adults

75% of patients have liver cysts by the seventh decade

Chromosome 16 mutation in PKD 1: Accounts for 85% of cases; carries highest risk of developing ESRD

Chromosome 4 mutation in PKD 2: Accounts for ~15% of cases; ESRD develops later than with PKD1

Autosomal recessive PKD (ARPKD)

More severe liver involvement than ADPKD

2.List some other manifestations of ADPKD.

Cystic disease

Liver, spleen, pancreas

Berry aneurysm

Risk of subarachnoid haemorrhage (SAH) if ruptures (treatment includes blood pressure [BP] control, lipid lowering and smoking cessation)

Pain/haematuria

If ruptured cyst, stone, infection or renal cell carcinoma

Renal cell carcinoma

Risk of malignant cyst transformation

Valvular disease

MVP, aortic valve disease

Hypertension

LVH

Gastrointestinal

Colonic diverticulum formation, herniae

3.What are the indications for nephrectomy in ADPKD?

Recurrent infections

Chronic pain

Recurrent haematuria

GI pressure symptoms, e.g. early satiety

Size/creating space for transplantation

4.List some other renal cystic disorders.

Unilateral

Benign renal cysts

Renal cell carcinoma

Polycystic kidney disease

Bilateral

Bilateral renal cell carcinoma

Amyloidosis

Von Hippel– Lindau syndrome (see below for further information regarding this condition)

Tuberous sclerosis

Von Hippel– Lindau syndrome

Autosomal dominant condition
Caused by mutations in the VHL gene (tumour suppressor gene)

Features

Angiomata develop in retina (may develop retinal haemorrhages and cause visual loss if left untreated), brain and spinal cord, liver, kidney and pancreas

Cerebellar haemangioblastoma (lateral lobes)

Phaeochromocytoma

Renal cell carcinoma

Endolymphatic sac tumors (tumours of the inner ear, causing hearing loss, tinnitus and balance problems)

Usually requires annual screening of eyes, kidneys and urinary peptides (for phaeochromocytoma), intermittent brain imaging

KEY POINTS

Look for any scars that may indicate a nephrectomy.

Look for any signs of renal replacement therapy.

Know the causes of cystic renal disease.

RENAL REPLACEMENT THERAPY

Please examine this patient’ s abdomen.

FINDINGS

General: Cushingoid appearance

Hands:

Evidence of finger-prick testing: Suggestive of diabetes (could be the cause of ESRD or have arisen post-transplant)

Fine tremor: Could signify tacrolimus toxicity

Arms: AV fistulae (radiocephalic [seen at the wrist], brachiocephalic [seen around the antecubital fossa] or brachiobasilic [palpable medially from around the antecubital fossa (ACF) to towards the axilla]): Feel for thrills and listen for a bruit to determine if still functional; look for fresh venepuncture marks. If there is no palpable thrill but a bruit is audible, this could signify a synthetic graft.

Face: Corneal arcus, gum hypertrophy (secondary to ciclosporin)

Neck/chest: Scars from internal jugular vein catheters, tunnelled-catheter exit site scar, parathyroidectomy scar (look carefully for this: it will be hidden in the crease at the base of the neck)

Abdomen:

Peritoneal dialysis catheter or scars from previous catheters (look for previous exit site scars: usually lateral to the umbilicus, and if removed, there may be a small longitudinal scar infra-umbilically).

Midline laparotomy scar or posterior subcostal scar: Evidence of previous nephrectomy (possibly bilateral).

Note that a midline laparotomy scar could also be present if the patient has had a simultaneous kidney– pancreas transplant (usually the renal graft is situated in the left iliac fossa in these patients).

Palpable mass in iliac fossa (graft may have been removed, so mass may not be palpable; scars can be very faint).

PRESENTATION

This patient has had a renal transplant as evidenced by the presence of a renal transplant in the right iliac fossa (RIF). This is a functioning transplant as the patient does not have evidence of recent dialysis (fistula not recently needled/no PD catheter present) or fluid overload.

Comment on the following:

Renal replacement therapy

Any other forms, e.g. vascular catheter, PD catheter, AV fistula (are they being actively used?)

Fluid status

Signs of fluid overload (raised jugular venous pressure [JVP], peripheral oedema)

Immunosuppression

Ciclosporin: Gum hypertrophy

Corticosteroids: Cushingoid features

Skin lesions: Suggestive of previous skin cancers/removals (squamous cell carcinomas [SCCs]/basal cell carcinomas [BCCs])

Try to link with a possible underlying cause for renal failure:

Diabetes

Injection sites on abdomen/lipodystrophy, pinprick marks on fingertips

ADPKD

Bilateral ballotable masses in flanks

Alport’ s syndrome

Hearing aids

MANAGEMENT

Maintenance immunosuppression usually consists of a calcineurin inhibitor (CNI) (tacrolimus or ciclosporin) and an antiproliferative (azathioprine or mycophenolate mofetil), with or without steroids.

Side effects include (this is not an exhaustive list of complications; see British National Formulary [BNF] for further details)

Tacrolimus (calcineurin inhibitor): Tremor, alopecia, diabetes, hypertension, renal impairment, renal failure, blood disorders

Ciclosporin A, as for tacrolimus except gingival hypertrophy, hypertrichosis, hyperlipidaemia,

Mycophenolate mofetil: Diarrhoea, nausea, vomiting, leucopenia, lymphopenia, anaemia, thrombocytopenia, foetal toxicity, infections, malignancy (especially skin)

Azathioprine: Hypersensitivity reactions, dose-related bone marrow suppression, liver impairment, infections, pancreatitis

Prednisolone: Thin skin, easy bruising, muscle wasting/weakness, diabetes, hypertension, osteoporosis, pancreatitis, infections, glaucoma, cataracts, heart failure

Rapamycin (mTOR) inhibitors (sirolimus, evorolimus): Hypertension, impaired healing, venous thromboembolism (VTE), interstitial lung disease, proteinuria, hyperlipidaemia, reversible male infertility

All these except prednisolone give an increased risk of malignancy.

Screening should be similar to that for the general population, e.g. breast, colon screening.

Annual skin checks should be undertaken with a dermatologist for signs of SCC and BCC.

QUESTIONS

1.What are the most common causes for a renal transplant?

Diabetes mellitus

Glomerulonephritis

ADPKD

Hypertension

2.What investigations would you request in a patient with a renal transplant admitted with a rise in serum creatinine?

Blood tests: Renal function, FBC, bone profile, LFTs, CRP if signs of infection + blood cultures/virology (e.g. CMV, BK virus polymerase chain reaction [PCR]), immunosuppression levels to check for toxicity

Urine: Dipstick (check for haematuria, proteinuria, leucocytes and nitrites), urine microscopy, culture and sensitivity, urine for quantification of proteinuria (if applicable), virology for BK virus

Ultrasound scan of the transplant with Dopplers of the vessels: To assess for obstruction, renal perfusion, possible renal artery stenosis and renal vein thrombosis

Transplant biopsy: If no other cause found, to rule out rejection and look for any other cause

3.What are the signs of a failing transplant?

Progressively declining renal function

Proteinuria

Tenderness over the transplant graft

Fluid overload

Interstitial fibrosis, tubular atrophy or vascular changes in a renal transplant biopsy

4.What do you know about the manifestations of Alport’ s syndrome (AS)?

Alport’ s syndrome is a genetic disease in which there is defective type IV collagen.

There are three main types – X-linked (the most common), in which males are more severely affected than females; autosomal dominant; and autosomal recessive

Manifestations

Kidneys

Initially presents with microscopic haematuria and then proteinuria develops. About 50% of males with X-linked AS require dialysis or transplantation by ~25 years and about ~90% by aged 40 years.

Ears

Sensorineural hearing loss

Eyes

Anterior lenticonus can lead to slow progressive visual loss.

Management

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to try to delay onset of ESRD

Hearing aids as needed

KEY POINTS

Look closely for any scars which may represent a renal transplant.

If there is a renal graft present, comment on whether you believe it is functioning.

Look for other forms of renal replacement therapy.

Know the common causes for a renal transplant and how to manage a patient presenting with acute transplant dysfunction.

REFERENCES

National Institute for Health and Care Excellence. (2016) British National Formulary. Available from https://www.evidence.nhs.uk/formulary/bnf/current/. Accessed 18 August 2016.

Renal Association. (2011) British Renal Association guidelines on the post-operative care of the kidney transplant recipients. Available from http://www.renal.org/guidelines/modules/post-operative-care-of-the-kidney-transplant-recipient#sthash.UPL7Z6si.dpbs. Accessed 18 August 2016.

Renal Association. (n.d.) Alport syndrome – Patient information. Available from http://rarerenal.org/clinicianinformation/alport-syndrome/. Accessed 18 August 2016.

SPLENOMEGALY

Please examine this gentleman’ s abdominal system.

FINDINGS

General: Pallor, purpura

Peripheral: Lymphadenopathy

Abdomen: Enlarged spleen

Be aware of how to differentiate splenomegaly from an enlarged kidney:

Features of a spleen: Mass in the left upper quadrant (LUQ) (moves towards RIF with respiration), unable to get above a spleen on examination, dull to percussion, nonballotable, presence of a palpable splenic notch

Features of a kidney: Moves minimally with respiration, can get above a kidney, resonant to percussion, ballotable, no notch palpable

PRESENTATION

This patient has evidence of splenomegaly as there is a palpable mass in the left upper quadrant which moves inferomedially with respiration. I am unable to palpate above it and there is also a splenic notch palpable. On peripheral examination, there is evidence of pallor and bruising. There is no palpable lymphadenopathy.

Look for other signs leading to the underlying cause of the splenomegaly:

Felty’ s syndrome

Rheumatoid hand signs

Portal hypertension

Signs of chronic liver disease

Infective endocarditis

Murmur, splinter haemorrhages

CML/CLL/lymphoma

Lymphadenopathy (CLL/lymphoma), pallor

Splenomegaly can be classified by the degree of enlargement (but remember that causes of massive splenomegaly may be moderate to start with):

Moderate enlargement (11– 20 cm)

Rheumatological disease

Rheumatoid arthritis, SLE, Sjogren’ s syndrome

Infection

Schistosomiasis, malaria, leishmaniasis, EBV

Haematological

Lymphoma, leukaemia, myeloproliferative disease, haemolytic anaemia

Massive enlargement (> 20 cm)

Myelofibrosis

Chronic myeloid leukaemia

Visceral leishmaniasis

INVESTIGATIONS

Bloods

FBC and blood film, haemolysis screen, LFTs, U&Es, CRP, blood cultures, malaria screen, virology for EBV, autoantibodies including rheumatoid factor

Biopsy

Bone marrow aspirate, lymph node biopsy, splenic biopsy

Imaging

USS abdomen, CT chest/abdomen/pelvis, echocardiogram if infective endocarditis suspected

MANAGEMENT

This is dependent on the underlying cause.

QUESTIONS

1.What is the function of the spleen?

Removal of old/damaged red blood cells

Storage of platelets

B- and T-lymphocyte-mediated immune function

2.What advice should be given to a patient undergoing a splenectomy?

Preoperative vaccinations: Pneumococcal, meningococcal, Haemophilus influenzae

Lifelong prophylactic penicillin

Annual influenza vaccinations

Wear a medic alert bracelet

Advice regarding seeking medical attention if unwell

3.What are the indications for a splenectomy?

Hypersplenism: Autoimmune destruction of blood cells (for example, idiopathic thrombocytopenic purpura [ITP])

Mass effect of spleen

Traumatic rupture

Haematological malignancies (rarely)

Congenital haemolytic anaemias: Hereditary spherocytosis, elliptocytosis

4.Tell me about PRV.

This is a primary polycythaemia, due to a fault in the bone marrow. It is the result of uncontrolled proliferation of mainly red blood cells, often due to a mutation in the Janus kinase 2 (JAK2) gene. Myeloid leucocytosis, thrombocytosis and splenomegaly can also occur.

PRV may present with a raised haemoglobin level on a routine blood test. It can also present with thrombosis (or more rarely, bleeding), headache, sweating and pruritus.

Investigation would initially be with a full blood count. Other (secondary) causes of polycythaemia should be excluded. If PRV is suspected, JAK2 mutation testing is carried out on a blood test. Imaging (CT/ultrasound) is used to visualise the spleen. Bone marrow biopsy is helpful for diagnosis.

Diagnosis is by the World Health Organization (WHO) diagnostic criteria 2008.

Management is targeted at lowering the risk of thrombosis. This includes venesection, aspirin and myelosuppression. JAK2 inhibitors are being introduced/under clinical trial. Management of symptoms such as pruritus should also be considered.

Alongside thrombosis, a major complication of PRV is transformation to acute myeloid leukaemia.

KEY POINTS

Be sure to measure splenomegaly to aid clinical diagnosis and be aware of how to differentiate between a palpable kidney.

Be sure to look for peripheral signs to identify an underlying cause.

REFERENCE

Tefferi A, Thiele J, Vardiman JW. (2009) The 2008 World Health Organization classification system for myeloproliferative neoplasms: Order out of chaos. Cancer 115(17): 3842– 7.

ABDOMINAL STATION SUMMARY

In this station, do not forget the normal abdomen. Remember the value of peripheral signs, e.g. lymphadenopathy; you may have your diagnosis before you lay your hand on the abdomen.

Don’ t forget to ask the patient if there is any pain in the abdomen before you begin palpation. This is basic, but it can be embarrassing if you hurt the patient, and in all likelihood will result in a fail.

Apologise if you cause the patient any discomfort.

If possible, establish a cause for the patient’ s organomegaly to demonstrate to the examiners that you are thinking one step ahead.

Demonstrate to the examiners that you are thinking ahead by inspecting for side effects of any treatments that the patient is receiving, e.g. the cushingoid patient with a renal transplant.

Positioning is very important; ensure the patient is flat when you palpate the abdomen.

Make your examination slick and quick, as you may run out of time before you finish it, but at the same time, don’ t be in a rush (a skill that can only be learnt with practice).

Try not to be put off by unusual opening statements, for example, ‘ Please examine this patient with hypertension’ (the opening statement will generally be relevant, e.g. a patient with renal disease/ESRD).

If you palpate an organ, always ensure that you percuss it.

Know how to clinically differentiate a spleen from a kidney (this is a PACES classic).

Do not make up any findings.