VIVA: Pathology - Endocrine Flashcards
What are the principal complications of diabetes mellitus?
- Vascular*:
- Macro: atherosclerosis, CAD, PVD, RAS, HTN and CVA
- Microangiopathic: thickened BM and increased permeability of capillaries to plasma proteins -> nephropathy, retinopathy, neuropathy - Pancreatic changes*:
- Loss of islet cells (number and size)
- Amyloid infiltration of islets - Renal:
- Sclerosis, BM thickening, glomerulosclerosis - Ocular:
- Proliferative and non-proliferative
- Haemorrhages
- Exudates
- Neovascularisation
- Detachment
- Glaucoma - Neuropathy
- Increased susceptibility to infections
- Metabolic:
- HONK
- DKA
- Hypoglycaemia
- Hyperglycaemia
*needed to pass + 3 complications
Outline some of the differences in patients with type 1 and type 2 diabetes
Type 1*:
- Typical onset during childhood (<18yo)
- Usually abrupt onset due to exhaustion of beta islet cell reserve, often with a precipitating illness increasing demands on pancreas (e.g. infection)
- Normal or underweight
- Decreased blood insulin
- Circulating islet autoantibodies
- Presents with polyuria, polydipsia, polyphagia +/- ketoacidosis
- Genetic linkage
- Dysfunction in T cell immunity resulting in islet autoantibodies
Type 2*:
- Typical onset during adulthood, often >40yo
- Overweight
- Often asymptomatic and incidental finding on routine follow-up or bloods
- Increased blood insulin (initially)
- No islet autoantibodies
- May develop hyperglycaemic hyperosmolar non-ketotic coma (HONC) with dehydrating precipitant (can also present with DKA less commonly)
- No genetic linkage
- Insulin resistance
- Often a longer course of illness due to residual pancreas capacity
- age + 2 clinical + 1 pathological feature to pass
What is the pathogenesis of type 2 diabetes mellitus?
- Insulin resistance*:
- Decreased ability of peripheral tissues to respond to secreted insulin
- Secondary to either genetic predisposition or obesity/lifestyle factors - Quantitative and qualitative beta cell dysfunction*:
- Manifests as inadequate insulin secretion in the face of insulin resistance and hyperglycaemia
- Initial beta cell hyperplasia maintains normoglycaemia with increased levels of insulin secretion
- Early and subsequently late failure manifests as impaired glucose tolerance and diabetes
- Genetic predisposition to B-cell failure
*needed to pass
What are the characteristic clinical findings of Grave’s disease?
- Clinical hyperfunction *
- Thyroid enlargement *
- Infiltrative ophthalmopathy
- Infiltrative dermopathy
*needed to pass
What is the pathogenesis of Grave’s disease?
- Autoimmune, involving a variety of Ab including auto-Ab to TSH receptors
- LATS (Long-Acting Thyroid Stimulator) IgG mimics TSH
How are pituitary adenomas classified?
- Classification based on hormone-cell type
- E.g. prolactin, growth hormone cell (densely or sparsely granulated), thyroid stimulating cell, ACTH cell, gonadotroph cell (including silent and oncocytic), mixed GH-prolactin cell, other plurihormonal cell, hormone negative
- May also be based on size: microadenomas (<1cm) vs macroadenomas (>1cm)
What clinical syndromes may be produced by a pituitary adenoma?
- Prolactinoma: amenorrhoea, galactorrhoea, loss of libido, inferility
- Somatotroph (GH): gigantism, acromegaly
- ACTH: Cushing’s syndrome
- Gonadotrophs: local effects (headache, visual impairment, diplopia, pituitary apoplexy), hypogonadism (lethargy, loss of libido, amenorrhoea)
What is thyrotoxicosis?
Hypermetabolic state caused by elevated circulating levels of T3 and T4
What are the clinical features of thyrotoxicosis?
- Cardiovascular *:
- Tachycardia
- Dysrhythmia
- CCF - Neuromuscular:
- Tremor
- Proximal myopathy - Ocular *:
- Wide staring gaze
- Lid lag
- Proptosis - CNS:
- Anxiety
- Emotional lability
- Insomnia - Skin:
- Warm, flushed
- Increased sweating - Heat intolerance *
- Thyroid storm *:
- Fever, tachycardia, arrhythmia
- May be fatal if not treated promptly
*needed to pass
What are the main causes of thyrotoxicosis?
- Diffuse toxic hyperplasia (Grave’s disease) *
- Toxic multinodular goitre
- Toxic adenoma/carcinoma
- Neonatal from maternal Grave’s disease
- Non-hyperthyroidism (e.g. thyroiditis)
*needed to pass + 1 other
What is the pathogenesis of diabetic ketoacidosis?
- Insulin deficiency * with glucagon excess
- Decreased peripheral utilisation of glucose with increased gluconeogenesis
- Results in severe hyperglycaemia * - Hyperglycaemia causes osmotic diuresis *, leading to dehydration
- Insulin deficiency increases lipolysis and production of FFAs *
- FFAs are converted to ketones by the liver *
- If rate of ketone body production exceeds rate of utilisation by peripheral tissues, ketonaemia and ketonuria results
- Decreased urinary excretion of ketones leads to systemic metabolic ketoacidosis
*needed to pass
What is the pathogenesis of type 1 diabetes mellitus?
3 needed to pass:
1. Genetic predisposition
2. Precipitating event:
- Exogenous antigen (viral), drugs
3. Autoimmune destruction of islet cells:
- Molecular mimicry or altered expression of beta-cell antigens
- 70-80% have auto-islet antibodies
- Beta-cell destruction leads to reduced cell mass and circulating insulin
4. Subclinical leading to overt DM:
- Hyperglycaemia
What environmental factors may contribute to the development of type 1 diabetes mellitus?
- Infections:
- E.g. group B coxsackieviruses, mumps, measles, CMV, rubella, EBV
- May induce tissue damage and inflammation, resulting in release of beta-cell antigens
- OR viruses produce antigens which mimic self-antigens with the immune response cross-reacting with self-tissue - Cows milk exposure prior to 4 months of age
- Drugs:
- E.g. pentamidine
How does genetic susceptibility contribute to the development of type 1 diabetes mellitus?
Complex pattern of genetic associations with putative susceptibility genes mapped to at least 20 loci:
- Most important is class II MHC (HLA), which accounts for 50% of total genetic susceptibility (on chromosome 6p21: HLA-D)
- 95% of Caucasians with type 1 diabetes mellitus have HLA-DR3, -DR4 or both
- Non-MHC genes include insulin and CTLA-4
What are the main adverse effects of acute severe sustained hyperglycaemia?
2 needed to pass:
1. Osmotic diuresis:
- Hypovolaemia, risk of thrombosis
2. Electrolyte losses:
- Na+, K+, PO4(3-)
3. Hyperosmolality:
- With changes in conscious state
