Case presentations and discussion in chronic liver disease and diabetes

1. Cases in General Medicine:
Session 4
Dr G Abraham

2. Case 1
• A 35 year old man with known alcoholism and
liver cirrhosis attends the ED with a 6 h history of
vomiting bright red blood.
• O/E
• Distended abdomen with shifting dullness.
• CVS, Resp, Neuro – nad.
• Obs: BP 85/62, pulse 110, T 37.6, sats 99% (air)
• What is the likely diagnosis and describe your
approach to management.

3. Case 1
• What are the causes of portal hypertension?
• How is symptomatic tense ascites managed?

4. Case 1 – Management of Variceal
Bleeding
• Airway management
• Volume resuscitation – fluid, blood products.
• Correct coagulopathy, FFP and Vitamin K
• Risk assessment (Blatchford/Rockall)
• Terlipressin 2 mg IV/6h
• Prophylactic antibiotics.
• Urgent endoscopy
• - Variceal band ligation, sclerotherapy

5. Blood Products
• Fresh frozen plasma if APTT/PT > 1.5 times
normal range.
• Offer cyoprecipitate if patient’s fibrinogen
remains low <1.5g/L
• Prothrombin complex concentrate to patients
on warfarin.

7. TIPS – Transjugular Intrahepatic
Portosystemic Shunt

8. Blatchford Score

9. Rockall Score

10. Portal Hypertension
• Obstruction of flow in
portal vein due to
increased intrahepatic
resistance leading to
collateralisation and
portal-systemic shunting.
• Collaterals are termed
varices commonly in
oesophagus derived from
left gastric vein.

12. Ascites
• A consequence of portal hypertension,
activation of renin-angiotensin system,
hypoalbuminemia.
• Results in clinical picture of abdominal
swelling, shifting dullness.
• Seen as a feature of chronic liver disease.
• Other causes include malignancy, congestive
cardiac failure, nephrotic syndrome.

13. Management of ascites
• Stop nephrotoxic drugs.
• Sodium restriction.
• Spironolactone
• Furosemide
• Diagnostic aspiration.
• Paracentesis in tense ascites.
• Albumin replacement in large volume paracentesis.
Fluid – send for:
Cell count
Total protein
Serum Ascites Albumin gradient

14. Case 2
• A 73 year old lady presents
to the GP with 6-9 months of
increasing thirst, polyuria,
weight loss of >3 kg and
intermittent blurred vision.
• Describe your approach to
assessment and
management.

15. Case 2 : Diagnostic steps in T2DM
Symptoms of diabetes
YES
Random venous glucose > 11.1
mmol/L
Fasting plasma glucose > 7 mmol/L
HbA1c > 48 mmol/L (6.5%)
NO
2 separate measurements
required
HbA1c reflects average
plasma glucose over the
previous eight to 12
weeks (not used in
diagnosis of T1DM)
Fasting
plasma
glucose >6.1,
<7.0
?

16. Glucose Tolerance Test
• Fast patient overnight
• Give 75 g glucose eg 350
ml Lucozade
• Test glucose after 2 h.
>11.1: Diabetes
>7.8 <11.1 : Impaired Glucose
tolerance

17. Case 2
• What is the next step in the patient’s
management?
• What drugs are used in the management of
type 2 diabetes?

18. Management of type 2 Diabetes – a
simplified approach
• Reinforce advice on diet, lifestyle and adherence to
drug treatment.
• Agree an individualised HbA1c target based on: the
person’s needs and circumstances including
preferences, comorbidities, risks from polypharmacy
and tight blood glucose control and ability to achieve
longer-term risk-reduction benefits.
• Measure HbA1c levels at 3/6 monthly intervals, as
appropriate. If the person achieves an HbA1c target
lower than target with no hypoglycaemia, encourage
them to maintain it.

19. Management of Type 2 diabetes
(Adapted from NICE guidelines)
Lifestyle measures ineffective and
HbA1C > 6.5 %, 48 mmol/L
Metformin
HbA1C >7.5%, 58 mmol/L
Add a second drug:
Sulfonylurea, Meglitinide, DPP4
inhibitor, Thiazolidinediones,
SGLT2 inhibitors

20. Management of Type 2 diabetes
Dual therapy ineffective
and HbA1c > 7.5%
Consider starting insulin: simplest starting
regime would be NPH insulin once daily
with metformin to continue. Start low and
titrate – most T2DM require 0.5-
0.7U/kg/24 hours
Mixed formulations may be useful.
Consider triple therapy. Eg Metformin, DPP4-
Inhibitors or Pioglitazone, Sulfonylureas
OR
Consider a
combination of
Metformin,
Sulfonylurea, GLP 1
mimetic as alternative
to insulin and
overweight.

21. Metformin
• Biguanides
• Mechanism – Decreases gluconeogenesis and
increases insulin sensitivity.
• Advantages – no hypoglycemia, lower incidence
of weight gain.
• Adverse effects – anorexia, nausea, vomiting,
diarrhoea, abdo pain, erythema, pruritus,
urticaria, B12 deficiency.
• Withdraw in conditions of dehydration, with
contrast infusion due to risk of lactic acidosis,
ketoacidosis, anesthesia, CKD > stage 3b

22. Sulfonylureas
• Oral drugs eg Gliclazide.
• Mechanism: Bind to ATP dependent 𝐾+
channel of pancreatic Beta cell. Increase
pancreatic insulin secretion.
• Adverse effects: Hypoglycemic episodes and
weight gain.
• Rare effects include SIADH, photosensitivity,
peripheral neuropathy, cholestasis.

23. Meglitinides
• Examples are Rapaglinide, Nateglinide.
• Similar mechanism to sulfonylureas.
• Used as an effective alternative due to lower
frequency of hypoglycemia.
• Associated with weight gain

24. Thiazolidinediones
• Examples are pioglitazone, rosiglitazone.
• Reduces peripheral insulin resistance – agonist
at PPAR gamma receptors involved in glucose
handling.
• Adverse effects recognised are heart failure,
bladder cancer and bone fractures.
• Associated with weight gain and liver function
derangement.

25. GLP1 and the incretin effect
• Glucagon-like peptide (GLP)-1 is a gut hormone that
stimulates insulin secretion, gene expression, and β-
cell growth.
• It is responsible for the incretin effect, the
augmentation of insulin secretion after oral as opposed
to intravenous administration of glucose.
• Type 2 diabetic patients typically have little or no
incretin-mediated augmentation of insulin secretion.
• The natural peptide is rapidly degraded by the enzyme
dipeptidyl peptidase IV (DPP IV)

26. DPP-4 inhibitors
• Examples are Sitagliptin, Vidagliptin.
• Oral drugs
• No incidence of weight gain.
• Used as an alternative to pioglitazone if weight
gain not desirable.
• Serious adverse reactions are acute pancreatitis
and hypersensitivity reactions.
• Headache is common and hypoglycemia reported
when used in conjunction with sulfonylureas,
insulin.

27. GLP1 mimetics
• Examples are Exenatide, Liraglutide
• Typically bd sc injections.
• Used as alternative to insulin at point in
algorithm where it would be considered.
• Typically causes weight loss.
• Use is limited by GI side effects, increased
incidence of acute pancreatitis, renal failure.

28. Types of insulin
Type of
action
Onset Peak Duration Example
Rapid 5-10 mins 30- 90 mins 2-4 hours Lispro, Aspart
(Novorapid)
Short 30 mins 1-2 hours 4-6 hours Soluble
insulin
(Actrapid)
Intermediate 2 h 3-6 h 18-24 h Isophane
Insulin/NPH
Long acting 1-3h Flat 12-24 h Insulin
Glargine,
Insulin
Detemir

29. Case 3
• An 18 year old presents with
shortness of breath and
abdominal pain.
• There is a 2 day history of
progressive confusion,
lethargy and malaise.
• ABG on air shows:

30. Diabetic Ketoacidosis
• Typical presentation with drowsiness,
vomiting, dehydration in a type 1 diabetic with
predictable triggers.
• Ketotic breath, severe dehydration, Kussmual
hyperventilation.
Venous pH Serum Glucose Blood/urine
ketones
Osmolality
<7.3 Variable usually
>11
>3 mmol/L
2+ ketonuria
variable

31. Management of diabetic ketoacidosis
• Fluids - 1-2 L N Saline/ 1-2 hours
• Then 4-8L over 1st 24 hours
• Second line with 5% dextrose once glucose <14
mmol/L
• Insulin – IV infusion Insulin fixed rate (see next
slide)
• Dose: 0.1 U/kg/h NOT SLIDING SCALE
• Titrate rate to targets Potassium – If K< 5.5 give
40 mmol/L 𝐾+
with fluids.

32. DKA – Monitoring and targets of
therapy
• Aim to reduce:
• CBG < 3 mmol/hour
• Blood ketones < 0.5 mmol/l/hour
• Increase venous 𝐻𝐶𝑂3> 3 mmol/L/hour
• If targets are not met, increase insulin rate by
1 U/kg/hour.
• Continue basal insulin

34. Case 4
• You are on call at night.
• The nurse has bleeped you to the ward to see
a patient with reduced conscious level.
• They have done a capillary BM showing 2.1
mmol/L.

35. Hypoglycemia
• ‘4 on the floor’
• Clinical features:
autonomic – sweating,
palpitations, dizzy,
neurological – confusion,
drowsiness, seizures, coma
• Treatment: Oral sugar,
orange juice, fruit jam,
toast
• Glucagon 1 mg IM
• 25 – 50 ml Glucose 50% IV

36. References
• Current management of the complications of portal hypertension: variceal bleeding and ascites. Dib, Oberti F,
Calès P.CMAJ. 2006 May 9;174(10):1433-43.
• https://pathways.nice.org.uk/pathways/acute-upper-gastrointestinal-bleeding
• https://www.diabetes.org.uk/Guide-to-diabetes/Managing-your-diabetes/Treating-your-diabetes/Tablets-and-medication
• https://pathways.nice.org.uk/pathways/type-2-diabetes-in-adults