Clinical application of non-Type I hypersensitivity reactions

Signs and symptoms of Myasthenia gravis

ptosis + diplopia

dysphagia

slurred speech

dyspnoea

weakness in arms/ legs that gets better with rest/ worse with use

What happens in myasthenia gravis?

How do you treat myasthenia gravis?

Acetylcholinesterase inhibitors (Pyridostigmine)

Inhibition increases local ACh conc in the synaptic cleft → prolonged action of released Ach → increased probability of successful conduction across the synapse

may use steroids and other immunosuppressants (CPT)

IVIG / Plasma exchange → helpful in a myasthenia crisis

What can happen if you over treat myasthenia gravis?

Cholinergic crisis

Salivation

Lacrimation

Urination

Diarrhoea

GI distress (cramping)

Emesis

What can happen if you under treat myasthenia gravis?

Myasthenic crisis

Respiratory arrest

Ventilation and removal of autoantibodies

What would the blood work look like in graves disease?

Free T3/4: high

TSH: low

Treatment for graves disease

Carbimazole → TPO inhibitor

Radioactive iodine

Thyroidectomy

Signs and symptoms of diabetic ketoacidosis (DKA)

Kussmaul breathing

Acetone breath

Polyuria, polydypsia, fatigue (common in diabetes mellitis)

Nausea, vomiting

Pathophysiology of Type 1 diabetes

• Islet cell autoantibodies (ICA)

• Autoantibodies to GAD (GAD65; glutamic acid decarboxylase)

• Autoantibodies to insulin, the tyrosine phosphatases IA-2 and IA-2b, and zinc transporter 8 (ZnT8)

CD8+ & CD4+ cells damage islet cells → ER stress, oxidative stress, inflammation

** type IV hypersensitivity

Treatment for type 1 diabetes

• Metformin: insulin sensitisers (decrease hepatic glucose production)

• Sulphonylurea (stimulate insulin secretion)

• GLP-1:glucagon peptide agonist (Stimulates insulin secretion, suppresses glucagon secretion + slows gastric emptying)

• SGLT2: (increase excretion of glucose through kidneys (renal glucose elimination))

Pathophysiology of post-streptococcal glomerulonephritis

Infection with nephritogenic strain of group A ß-hemolytic streptococ streptococci → different surface M protein → immune complexes

** type III hypersensitivity

Note rheumatogenic strains → can cause Rheumatic fever

** Streptokinase no longer used as a fibrinolysis →