Diabetes and the eye👀

Types of eye pathology associated with diabetes:

Glaucoma: earlier debut is noticed in patients with DM.
Symptoms typical of acute glaucoma include an acutely red, painful eye with reduced vision. Occurs when new blood vessels hm grow in the iris and block the drainage of fluid.

Rubeotic glaucoma occurs when new blood vessels that are abnormal grow on the iris and block the drainage of fluid, leadingsecondary to raised intraocular pressure. High intraocular pressure can cause headache, nausea, and vomiting.

Diabetic retinopathy that is uncontrolled and proliferative is a common cause of rubeotic glaucoma

Bilateral diabetic papillopathy: a reduction in visual acuity that is sudden, does not fluctuate, and does not improve with a pinhole. A relative afferent pupillary defect may be present if one eye is affected more severely than the other. Direct ophthalmoscopy would reveal swollen discs.

Bilateral macular oedema (exudate within the macula) presents as a a gradual decline in central vision. Some patients describe missing patches of text when they read. 

Variable refractive change:  it is caused by fluctuations and rapid reduction of blood glucose that may alter the composition and thickness of lens (lens hydration). It may manifest with:blurred  vision when driving, watching TV,   reading 

Bilateral cataracts: patients with DM tend to develop cataract earlier than those without DM. It results in a gradual decline in vision.

They classically cause patients to experience a glare with oncoming headlights while driving at night.

Vitreous haemorrhage may occur in patients with diabetes who have proliferative retinopathy (when retinal tissue becomes hypoxic new blood vessels form - proliferative diabetic retinopathy). Bleeding occurs from new vessels at the optic disc or elsewhere. 

Screening for retinopathy should be done in the begging (when DM 1 or 2 is diagnosed) and every 2 years afterwards.

Diabetes mellitus - diagnosis -

Variceal bleeding

TO DO LIST

1. Fluid resuscitation to a target mean arterial blood pressure of 65 mmHg: Ringer acetate.
2. Plan for urgent endoscopy.
3. Intravenous terlipressin 2 mg four times a day  (in patients without a history of ischaemic heart disease or peripheral vascular disease).
4. Blood transfusion given if the haemoglobin falls below 7 g/dL, to a target of 8 g/dL.
5. Nasogastric sond.
6. Consider PPI i.v. ( esomeprazol or pantoprazol) 80 mg bolusdos and after that  infusion 8 mg/h i 72 hours. 
7. Consider reversal of anticoagulation (Ocplex) 1500 IE (10-30 IE/kg)  or Confidex, Konakion 10 mg i.v. 
8. Antibiotic profylax (reduces the risk of repeat bleeding, spontaneous bacterial peritonitis).

Resources:

Jairath V, Rehal S, Logan R, et al. Acute variceal haemorrhage in the United Kingdom: patient characteristics, management and outcomes in a nationwide audit. Dig Liver Dis 2014;46(5):419-26.

Acute liver failure

What happens in acute liver failure?

Acute liver failure  is a deteriorating of liver functions that results in:

1. Coagulopathy, usually with an international normalized ratio (INR) of greater than 1.5. Causes: impaired liver protein synthesis.
2.  Encephalopathy - because of impaired ammonia clearance.
3. Hypoglycemia - because of impaired glyconeogenese.
4. Jaundice- impaired bilirubin metabolism
5. Lactic acidosis - impaired lactate clearance. 
6. Ascites - impaired albumin synthesis 

Dyspepsia - red flags -

Etiology:

• Peptic ulcer or  malignancy
• Gastro-oesophageal reflux disease (GORD)
• Hiatus hernia
• Coeliac disease ( gluten intolerance, test for IgA-transglutaminas(tTG)-antibody)
• Crohn’s disease
• Gastroparesis
• Medications: eg non-steroidal anti-inflammatory drugs (NSAIDs), bisphosphonates (such as alendronic acid or risedronate), iron supplements, nitrates, levodopa
• Pancreaticobiliary disease eg gallstone disease, pancreatic malignancy
• Systemic conditions eg diabetes, Addison’s disease. 

Red flags with indication for further investigation:

• Age greater than 55 with new onset dyspepsia
• Dysphagia
• Unintentional weight loss ( then  order an endoscopy as soon as possible < 2 weeks)
• GI bleeding
• Trombocytose
• Persistent vomiting
• Iron deficiency anaemia
• A palpable epigastric mass
• An abnormal barium meal result

Investigation: endoscopy, if negative then CT abdomen : pancreatobiliary disease, gallstone or malignancy?

Resourses: BMJ learning

Liver function tests

What kind of liver abnormality does the patient have:

• Isolated bilirubin?

• Cholestatic?

• Hepatitic?

1. Isolated raised bilirubin: Most commonly caused by Gilbert’s syndrome (affects 8% of the population); consider haemolysis in patients with anaemia.
2. Cholestatic: Predominantly raised ALP (alkaline phosphatase) and GGT (gamma glutamyltransferase) indicate cholestasis. Common causes include: primary biliary cirrhosis, primary sclerosing cholangitis, biliary obstruction (stones, strictures, neoplasia etc), and drug induced liver injury
3. Hepatitic: Predominantly raised ALT (alanine transaminase) and AST (aspartate aminotransferase) indicate hepatocellular liver injury (hepatitis). Common causes include: viral hepatitis, non-alcoholic fatty liver disease (NAFLD), alcohol related liver disease (ARLD), autoimmune hepatitis, and drug induced liver injury.

 Elevated GGT?

Alcohol consumption, drug induced liver injury, NAFLD, cholestatic liver disorders, liver metastases, hepatic congestion secondary to heart failure.

 ELEVATED GGT and ALP?

Elevated GGT and alkaline phosphatase (ALP) with normal or less pronounced elevations of ALT or AST is suggestive of a cholestatic disorders: gallstones, pancreatic cancer, cholangiocarcinoma, primary biliary cirrhosis, primary sclerosing cholangitis, or drug induced liver injury.

The description of pale stools, dark urine, and itching is characteristic of post hepatic jaundice.

ELEVATED TRANSAMINASE?

In alcohol related disease, AST tends to rise higher than the ALT. In alcoholic hepatitis and cirrhosis, the AST/ALT ratio is greater than 2 in around 70% of patients.
In alcoholic hepatitis, serum AST levels rarely rise above 500 iu/L and ALT rarely rises above 300 iu/L. In comparison, acute infectious hepatitis and drug and toxin injury often cause much higher ALT and AST rises.

In patients with NAFLD (non-alcoholic fatty liver disease), the typical abnormality is mildly raised serum ALT and/or GGT levels.

ELEVATED FERRITIN AND LIVER DISFUNCTION?

Raised ferritin with normal saturation < 45 % and a raised corpuscular volume (MCV) is suggestive of ARLD.

Hepatic function	Clinical feature in acute liver failure
Bilirubin metabolism	Jaundice
Gluconeogenesis	Hypoglycaemia
Ammonia clearance	Hepatic encephalopathy/cerebral oedema
Lactate clearance	Lactic acidosis
Protein synthesis	Coagulopathy
	Neutrophil dysfunction, risk of sepsis
	Ascites

Resources:

• http://learning.bmj.com/learning/modules/flow/JIT.html?execution=e1s3&moduleId=10054395&status=LIVE&action=start&_flowId=JIT&sessionTimeoutInMin=90&locale=en_GB&shouldStartAtQuestionSection=false&page=2
• Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for nclinicians. CMAJ 2005;172(3):367-79.
• Jonston DE, Special considerations in interpreting liver function tests, Am Fam Physicians 1999; 59(8), 2223-30

Decompensated liver disease and acute kidney failure

• It is more common in association with spontaneous bacterial peritonitis. 
•  Search for causes: nefrotoxic,  infection?Perform urinalysis and urine culture, looking for infection or evidence of parenchymal kidney injury. 
• Withdraw diuretics and nephrotoxic drugs.
•  Euvolaemia should be achieved with albumin or a crystalloid.
•  If renal function in a patient with cirrhosis and ascites deteriorates despite initial treatment, the most likely cause is hepatorenal syndrome: Terlipressin and albumin treatment improves renal perfusion. Reduction in the effective circulating blood volume and  hypoperfusion of the kidney is the  underlying pathogenetic mechanism for the development of hepatorenal syndrome.

Terlipressin is a vasopressin analogue that generates vasocontrction . It ncreases mean arterial pressure and systemic vascular resistance; while the heart rate, cardiac output, HVPG and portal venous blood flow decrease significantly. This decrease correlates well with the decrease in plasma renin activity. 

The improvement in hemodynamics with Terlipressin is associated with an increase in glomerular filtration rate and deactivation of the vasoconstrictor and sodium-conserving hormones with reduced activity of the RAAS resulting in increased natriuresis. Patients with HRS who show an improvement in renal function with Terlipressin and albumin seem to have an excellent post-transplantation outcome similar to that of patients without HRS. 

BMJ 2016;352:i124 doi: I/bmj.i124 (Published 26 January 2016)

J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:109-14. doi: 10.1111/j.1440-1746.2010.06583.x.

Acute pancreatitis - The essentials -

Acute pancreatitis is inflammation of the pancreas. The pancreas is "eaten" by the enzymes that it produces.

Causes: ususally gallstones, alkohol, hypertrigliceridemia, viral infections (coxackie, mumps - epidemic parotitis).

Diagnosis: abdominal pain and vomiting  associated with increase in serum amylase or lipase levels at least mare than three times upper limit of normal. Lipase levels remain increased for longer than amylase levels.

Acute pancreatitis is diagnosed when at least 2 of 3 criteria are present:

• typical abdominal pain, 

• raised enzyme levels, 

• appearances of pancreatitis on computer tomography.

Blog tests may reveal hypercalcemia and hypertrigliceridemia

Abdominal US may reveal gallstones.

Differential diagnoses: 

• Perforated peptic ulcer, 

• Myocardial infarction

• Cholecystitis.

Medical management

• Ringer lactat 2,5-4 l the first 24 h or enough to get a normal urine output 0.5-1ml/kg/hr.
• Antibiotics? Only if infection is clinically suspected or found.At present there is no indication for early antibiotics to prevent infection pancreatic necrosis.
• Pain relief (opioid) 
• Enter nutrition - nasogastric intubation.

Source: BMJ 2014;349:g4859 doi: 10.1136/bmj.g4859 

Travelers diarrhoea - how to avoid it -

Travelers diarrhoea - how to avoid it -

Source: BMJ Clinical review

BMJ 2016;353:i1937 doi: 10.1136/bmj.i1937

1.  Boiling water, cooking food Thoroughly, and peeling fruit and vegetables.  
2.  Avoiding ice, shellfish, and condiments on restaurant tables.
3.  Using a straw to drink from bottles, and avoiding salads and buffets where food may have been unrefrigerated forsevera hours. 
4. Drink bottled water where available, including in alcoholic drinks, as alcohol does not sterilise non-bottled water. If bottled water is not available, water can be purified by boiling, filtering, or use of chlorine based tablets.
5.  Use alchohol hand gel may reduce diarrhoea rates in travellers.
6.  Hand washing with soap reduces the risk of diarrhoeal illness by 30-40%.

If you've got it anyway, use rehydration salts (or a mixture of six level teaspoons of sugar and half a teaspoon ofsalt in a litre of clean water if rehydration. 

salts are unavailable) (see http://rehydrate.org/rehydration/index.

html).

Loperamide (anti motility agent)  might be of help, but it should be  avoided in
the presence of severe abdominal pain or bloody diarrhoea which can signify invasive colitis.

Investigations (for diarrhoeal symptoms that persist beyond 14 days following
travel or sooner if there are other concerning features such as
fever or dysentery):

• full blood count,
•  liver and renal function,
•  inflammatory markers;
• stool samples for microscopy and culture; and examination for ova cysts, and parasites. 

The most common cause of long lasting diarrhoea after traveling is Giardia, easy treatable with 5 nitroimidazole, tinidazole 2 g once only or metronidazole 400 mg three times daily for five days.