Cholangitis

Inflammation of the biliary tree

Cause

As with Cholecystitis, cholangitis is usually a complication of gallstones and/or surgery or scoping of the biliary tree. Obstruction of the biliary tree by malignancy can also cause cholangitis.  It can carry significant morbidity/mortality, particularly if it does not respond to antibiotic treatment (toxic cholangitis).

In the UK, the most common infective organisms are Klebsiella spp., E coli, Enterobacter spp., enterococci and streptococci.  Infection may be mixed.  Outside the UK, parasitic infection by roundword and liver fluke can also cause cholangitis.

Presentation

• Charcot’s triad
  • Fever (90%)
  • RUQ pain and tenderness (70%)
  • Jaundice (60%)
• Reynaud’s Pentad
  • Charcot’s triad + Hypotension (shock) + Mental confusion
  • Severe disease i.e. affecting one or more of the vital organs
• Other symptoms include chills/rigors; nausea and vomiting

Investigations

• Lab tests
  • FBC- Raised WCC; CRP
  • LFTs- Raised Alk Phos and Bilirubin (also may have deranged liver enzymes)
  • Serum Amylase may be raised
  • Blood cultures (positive in around 50%)
  • U&Es- any associated kidney failure
• Imaging
  • USS and/or MRCP and/or CT
    • Biliary dilation
    • Evidence of stricture/tumour/stones etc
• Drainage for culture (if done)

Diagnosis

1. Systemic Inflammation
   1. Fever/chills/rigor
   2. Lab info- raised WCC/CRP
2. Cholestasis
   1. Jaundice
   2. Lab info- deranged LFTs
3. Imaging
   1. Biliary dilation
   2. Evidence of underlying cause

• Suspect diagnosis if there is one point in 1. and one in either 2 or 3.
• Definite diagnosis if one from all 1, 2 and 3.

Management

• Fluid resuscitation
  • Resuscitation may be required for those patients in shock
  • ABCDE approach- manage any hypotension, tachycardia etc first
• Correct any coagulopathy (if necessary and possible)
• IV antibiotics (Amoxicillin and Metronidazole- consult local formulary)
• Endoscopic biliary drainage is recommended

Cholecystitis

Inflammation of the gallbladder

Causes/Aetiology/Risk Factors

• Most common cause is due to gallstones (Cholelithiasis) in the cystic duct.  Around 5% of cases are acalculous and are usually a complication of more severe disease/trauma.
  • e.g. after major surgery; severe trauma; sepsis; unusual infections in the immunocomprimised patient etc
• Risk factors include age, female sex, obesity, rapid weight loss, pregnancy, Crohn’s disease, hyperlipidaemia, diabetes, family history, certain drugs (oestrogens; ceftriaxone; narcotic withdrawal; anticholinergics etc)

In calculous cholecystitis, obstruction of the cystic duct leads to distention of the gallbladder and bile stasis.  This predisposes the gallbladder to infection by colonic bacteria e.g. E coli and bacteroides and also causes reduced blood flow and lymphatic drainage and subsequent mucosal ischaemia and necrosis.

Presentation

• History
  • Sudden onset, colicky or constant (early or late, respectively); severe pain in the upper right quadrant
  • May be associated with anorexia, nausea, vomiting, sweating
  • NB Elderly patient may not present with classical features, but may have vague symptoms like nausea and vomiting
  • History of gallstones
• Examination
  • Low grade fever may be present (a high temperature is uncommon); as may a mild tachycardia
  • Tenderness in the right upper quadrant
    • Murphy’s sign
      • Push your hand up into the right upper quadrant and ask the patient to breathe in.  If this is acutely painful, they are Murphy’s sign positive.
  • Evidence of severe disease/complications include
    • A palpable mass in the RUQ- usually in severe disease due to size of gallbladder
    • Jaundice may or may not be a sign of severity, but may be present in 10-15%

Investigations

• Blood work
  • FBC- White cells; CRP
  • Serum Amylase (always do this after an ERCP investigation- to assess any damage to the pancreas)
  • LFTs- Alk Phos is an indirect marker of cholestasis (often raised in disease of the biliary tree); bilirubin may also be raised in patients with cholecystitis.  ALT/AST is usually normal (more a marker of liver disease) but may be elevated if stones have blocked the common bile duct.
• Ultrasound of the gallbladder is usually the first mode of imaging used.  CT may also be used but more likely to be second line either if stones were not seen on USS or if surgery is thought to be required.
• MRCP is the gold-standard for imaging the bile duct and identifying stones/inflammation
• Endoscopic Retrograde Cholangiopancreatography (ERCP)- This is a very useful investigation because you are able to stent the bile ducts to help relieve some of the symptoms.

Management

• Admit someone with suspected acute cholecystitis for confirmation of the diagnosis; monitoring; treatment (see below) and surgical assessment
  • NB The patient will not require admission if they are not acutely unwell.  For gallstones without cholecystitis (either with mild intermittent symptoms or completely asymptomatic), patients should be routinely referred to GI/Hepatology.
• IV fluids should be given if required
• Antibiotic treatment of IV Amoxicillin and Metronidazole (according to NHS Tayside formulary) can be given to patients with acute disease who have severe symptoms
• Analgesia should be given
  • NSAIDs can be good (NB BEWARE of misdiagnosis of peptic ulcer where these are contraindicated)
  • If pain is severe, pethidine IM may be considered (according to NICE)
• Ultimately, cholecystectomy is definitive treatment.

Blunt Injury to the Eye

This usually occurs in sporting accidents e.g. football to the eye or from fights/assaults.  If it is a large object, the orbit will usually absorb most of the impact:

 

• Close inspection/palpation of the orbit should be done to rule out any blowout fracture (if suspected, a CT may be required)

 

If the blunt object is smaller, or if the force of a big object is large, the globe may take some impact.  Haemorrhage may occur, and can sometimes be seen as hyphaema (a collection of blood in the anterior chamber).

• The severity of hyphaema can be graded:
  1. Layered blood occupying less 1/3 of the anterior chamber
  2. > 1/3 but < 1/2
  3. > 1/2
  4. Total (or blackball, 8-ball)
• The main concern about hyphaema is a rise in intra-ocular pressure, which occurs in most cases due to blockage of the trabecular meshwork with erythrocytes and fibrin.
  • IOP may be high initially, then subsequently falls (can appear normal) due to < aqueous production and development of uveitis.  This can sometimes cause further haemorrhage and a secondary haemorrhage and rise in IOP (often more concerning)
• Mild grade 1 hyphaemas often don’t require any treatment- blood will be reabsorbed and the eye should recover.  More severe and any recurring haemorrhage will probably require bed rest, pressure control (beta-blocker), mydriatics and patching (steroid drops may also be required to reduce any secondary inflammation).

Any patient with visual loss following blunt injury should be referred and investigated.  Patients may also incur haemorrhage in the vitreous humour (vitreous haemorrhage) which can increase the chance of subsequent retinal detachment.  The patient may also develop synechia(e) and are at increased risk of developing traumatic glaucoma.

 

Prostate Cancer

Background

• Most commonly diagnosed male cancer (excluding skin) in the UK
• More common in older men- mean age ~72
• Carries significant mortality (71% 5 year survival- 4th most common cause of death in men)

Aetiology

• Hormonal factors
  • Like BPH, testosterone and dihydrotestosterone stimulate growth of the prostate and prostate cancers
• Genes
  • There are a few genes that have been specifically associated with hereditary forms of prostate cancer e.g. PCAP and HPC1
• Age
  • Largest risk factor- up to 67% of men >90 will have prostate cancer
• Race
  • Prostate cancer is more common in Black and Caucasian patients compared to Asian populations (possible dietary factor e.g. oestrogens naturally found in food; or vit D)

Pathophysiology

• The majority of prostate cancers are adenocarcinomas (>95%)
  • most arise in the peripheral zone (75%) and can be palpated as hard nodules.  The remainder mostly arise in the transition zone (20%)
  • Most cases have multifocal disease i.e. there are several distinct cancer lesions in the prostate (mean ~7)
• Prostate cancer invades locally through the prostate capsule and into the surrounding tissues (locally advanced disease)
  • This often occurs along the autonomic nerves that innervate the prostate (i.e. perineural spread)
• Prostate cancer can also metastasise, although the mechanism  behind this is poorly understood.  The most common site of spread is bone (particularly the axial skeleton)- and cause sclerotic lesions.
• Genetic changes frequently occur in prostate cancer.  Common genetic changes are hypermethylation of GSTP1 (detoxifying enzyme); rearrangement of Ch21 with fusion of androgen dependent protease TMPR552 and transcription factors (which then become androgen-dependent); PTEN is also frequently mutated

Grading Prostate Cancer – Gleason Score

Gleason grade Lower grades are associated with small, closely packed glands. Cells spread out and lose glandular architecture as grade increases. Gleason score is calculated from grade as described in the text. (Photo credit: Wikipedia)

• The Gleason score is an important prognostic indicator in prostate cancer
• It is calculated by adding the scores of the two most ‘common’ appearances within a biopsy- so the best score is 2 and worst is 10
  • Between 2-4 is well-differentiated; 5-7 is moderately differentiated and 8-10 is poorly differentiated
  • NB it can be useful to know the individual scores because if the predominant grade is worse, the prognosis could be also (e.g. 3+5 is better than 5+3).  The Gleason score can also be affected by treatments for prostate cancer, BPH and other androgen treatments and so should be interpreted with caution.
  • Prostate cancer is also staged using the TNM staging system

Presentation

• History
  • Localised prostate cancer
    • Asymptomatic (abnormal PSA/DRE)
• • LUTS (in most cases due to co-existent BPH) & erectile dysfunction
  • Haematospermia/haematuria/dysuria (probably due to coexistent BPH/prostatitis)
  • Locally advanced prostate cancer
    • Asymptomatic
    • As above but may also have symptoms of ureteric obstruction (i.e. a degree of renal failure)
  • Metastatic disease
  • As above (including asymptomatic)
  • Bone pain (particularly back/shoulder pain); pathological fracture
  • Peripheral oedema/leg swelling due to lymphatic spread
  • Anorexia, weight loss
  • Neurological symptoms of lower limbs (spinal cord compression)
  • Anaemia
  • Dyspnoea, jaundice, bleeding tendency
• Examination (DRE)
  • Most prostate cancer should be palpable on DRE
    • Hard, nodular, craggy, enlarged (cf soft, smooth and uniform)

Investigations

• PSA (Prostate specific antigen)

PSA testing should be offered to:

Men older than 50 who request a PSA test

Men with unexplained symptoms that could be caused by locally advanced or metastatic prostate cancer

Men with LUTS that could be caused by BPH or by prostate cancer

• Used in combination with DRE (and Gleason score once done) to predict likelihood of prostate cancer (and the pathological stage)
• • If DRE is abnormal and PSA >4, there is a 45% chance of diagnosis, which rises to >75% if PSA >10.
  • PSA tends to increase with advancing stage and tumour volume
• • i.e. if the PSA falls without any treatment, this is unlikely to be cancer
  • PSA is often a useful marker of disease progression/response to treatment

• Transrectal ultrasound of prostate (TRUSP) usually with biopsy
  • Several core samples are taken for grading
• Imaging (CT; PET CT and MRI)
  • In order to stage prostate cancer accurately, imaging is required
  • Bone PET scanning may be used if bone abnormalities/symptoms are detected after initial CT

Management

• Men with low-risk localised prostate cancer should be offered active surveillance
  • Any patient with a change in PSA or symptoms should be offered radical treatment
  • Active surveillance will involve regular PSA and follow up (usually 6 months-1 year, but this will depend on the individual case)
• Whilst active surveillance is also an option for intermediate risk disease, these patients, and those with high risk localised disease should be offered radical prostatectomy or radical radiotherapy
  • Hormonal treatment is recommended for minimum of 2 years in men receiving radical radiotherapy who have a Gleason score >7
• For men with locally advanced prostate cancer
  • Radical radiotherapy
  • Hormone therapy should be given to all men treated with radical radiotherapy for 3-6 months (2 years if gleason >7)
• Metastatic disease
  • Hormone therapy
  • Palliative care

Hormone therapy

• Luteinising hormone releasing hormone (LHRH) and gonadotrophin releasing hormone (GnRH) analogues (goserelin and degarelix, respectively)
  • Effectively shut-down LH release in response to LHRH overload.
  • However, in the first 4-6 weeks, there will be an initial spike in LH production and thus testosterone production (in the prostate and testes) which can stimulate tumour growth (both in the prostate and metastases)
    • Anti-androgens should be given in conjunction to prevent this (e.g. bicalutamide)

 

Subconjunctival Haemorrhage

A subconjunctival haemorrhage is caused by bleeding of the small, fragile conjunctival vessels.  It is usually secondary to some kind of trauma/stress to the vessels e.g. injury, sneezing/coughing, straining (e.g. childbirth, constipation) etc.  Blood is taken up from the subconjunctiva very slowly, and so any blood is collected within this space.

Blood thinners and hypertension are thought to increase the risk of subconjunctival haemorrhage.

It is usually presents with localised redness, which is well demarcated.  There is no pain or visual loss.  A diagnosis of foreign body in the eye should be excluded.

SCH is usually self-limiting and requires no treatment.  Underlying hypertension and/or blood-thinning/anticoagulation should be managed appropriately to reduce further risk.

Red eye

Red eye is one of the most common ophthalmic problems presenting to GP.  There is a potentially long differential diagnosis list for red eye, but an accurate history and examination can usually determine the cause and management. Presentation

• Ask about pain and visual loss which are suggestive of more serious conditions like:
  • corneal ulceration
  • iritis
  • acute glaucoma
• Ask about discharge
  • if purulent- suggests bacterial conjunctivitis
  • if clear (may be mistaken for tears)- suggests a viral/allergic conjunctivitis
• A gritty sensation is common in conjunctivitis but a foreign body in the eye must be excluded
• Itching is common in
  • Allergic eye disease
  • Blepharitis
  • Topical drop sensitivity
• It may also be useful to differentiate (on examination) between ciliary and conjunctival injection
  • ciliary injection involves branches of the anterior ciliary arteries and indicates inflammation of the cornea, iris or ciliary body.
  • conjunctival injection mainly affects the posterior conjunctival vessels, which are more superficial (so look more red), move with the conjunctiva and constrict with the application of topical vasoconstrictors

Examination and Investigation

• Check visual acuity; extraocular movements; pupillary reflexes (and any photophobia)
• Slit-lamp examination with fluoroscein should be performed to exclude any abrasions/ulceration etc
• Intra-ocular pressure would be important if glaucoma is suspected

Differential Diagnosis

• Bacterial conjunctivitis (I stupidly did two posts on this 1 & 2)
• Viral conjunctivitis
• Allergic conjunctivitis
• Glaucoma (see open-angle and closed-angle)
• Episcleritis/Scleritis
• Uveitis
• Corneal ulceration (keratitis)/ abrasion 
• Foreign body in the eye / trauma to the eye (either penetrating or non-penetrating)