Endocrine system I (a) Flashcards
Hyperglycemia resutls from?
(high blood sugar) defects in insulin
secretion, insulin action, or both
diganosis of Diabetes Mellitus
1) fasting blood sugar of ≥ 126mg/dL or,
2) Random blood glucose conc. of ≥ 200mg/dL, [with classical signs and symptoms] or,
3) Abnormal oral glucose tolerance test, with a
glucose concentration of ≥ 200mg/dL, two hours
after a standard carbohydrate load
*
The 5 major complications of Diabetes Mellitus (give examples)
1) Retionopathy (Cataracts, Galucoma)
2) Nephropathy (Glomeroulonecrosis, pyelonephritis)
3) Neuropathy (peipheral-nerves / autonomic-bladder)
4) microangiopathy (Hemorrhage, cerebral vascular infarcts-stroke)
5) Macrovascular disease (Atherosclerosis, MI)
*
clinical features of Diabetes Mellitus
-
“Honeymoon period”: First 1-2 years after
manifestation of overt type 1 diabetes - Hyperglycaemia
- Glycosuria –> Osmotic Diuresis –> Polyuria
- Polydipsia (increased thirst)
- Polyphagia (excessive hunger)
- Ketoacidosis (severe cases) [type 1 DM]
- Hyperosmolar non-ketotic coma (sever dehydration) [type 2 DM]
- Weight loss [type 1 DM]
- Obesity [type 2 DM]
honeymoon : pancreas is still able to produce small amounts of insulin
Epi + Primary defect of Type 1 Diabetes
- Autoimmune T-cell mediated destruction of pancreatic β-cells
- absolute insuline deficiency
Epi : < 20 yrs
Epi + Primary defect of Type 2 Diabetes
- increase in Insulin resistance
- progressive pancreatic β-cell failure
- realitive insuline deficiency
Epi : > 40yrs , overweight patients
Histology of Type 1 vs Type 2 diabtes Mellitus
Type 1: “insulitis” ; Islets lymphocytic infiltrates (made up of macrophages and lymphocytes)
Type 2: Islet Amyloid polypeptide (IAPP) deposists
Type 1 vs Type 2 diabetes
Explain the mechanisms responsible for β-cell dysfunction and insulin resistance in Type 2 DM
1) Free fatty Acids (FFAs) –> cause β-cell dysfunction –>
2) Induces insulin resistance in target tissues –>
3) Induce secretion of Pro-inflammatory Cytokines
Explain the Pathology of how islets are replaced by Amyloid in Type 2 DM
1) inadequate compensation for peripheral resiatnce –> Hyperglycaemia + loss of β-cell mass
2) Excess FFAs and glucose –> lymphocytic infiltration (Recruitment of macrophages and T cells) –> Cytokine production –> Beta cell dysfunction and death
3) Replacement of islets by amyloid
what is the normal body mechanism to increased insulin secretion
increased insulin secretion –> Compensation for Peripheral resistance –> Maintenance of normal plasma glucose
NOTE: diabetic pateints have Inadequate (insufficient) compensation for peripheral resistance
list 4 Diabetic Macrovascular diseases
1) MI
2) Atherosclerosis of the aorta and large/medium-sized arteries
3) Gangrene of the lowere extremities
4) Hylaine Arteriosclerosis [associated with hypertension]
list 3 complications of Diabetic Microangiopathy
1) Diabetic Nephropathy (Glomerulosclerosis, Pyelonephritis, Hylaine Arteriolosclerosis)
2) Retinopathy (cataracts, Galucoma)
3) Neuropathy (nerve injury in the legs and feet)
Diabetic Nephropathy
poorly controlled diabetes can cause damage to blood vessel clusters , leading to Glomerular lesions –> kidney damage. Explain how this happens
Changes in the apperance of the glomerulus due to lesions:
GBM thickening –> Mesangial expansion (Diffuse mesangial sclerosis) –> Nodular glomerulo-sclerosis (Kimmelstiel-Wilson lesions) –> Diffuse glomeurlosclerosis (chronic)–> kidney damage due to Ischaemia
* GBM : Glomerular Basement Membrane
Kimmelstiel-Wilson Lesion is aka?
Nodular Glomerulosclerosis
- Ball-like deposits, at the glomerular periphery
ocular complications of Diabetes
i. Retinopathy (Proliferative/ Non-proliferative)
ii. Cataract formation
iii. Glaucoma
Non-proliferative vs Proliferative Diabetic Retionopathy
Non-proliferative
–> Microangiopathy,retinal haemorrhages and exudates (“soft” = microinfarcts, “hard” = deposits of plasma proteins and lipids), micro-aneurysms and oedema
Proliferative:
–> Process of neovascularisation and fibrosis; Vitreous haemorrhages, due to rupture of newly formed vessels –> Organisation of the haemorrhage –> Retinal detachment
*Vitreous Haemorrhage : presence of blood in the vitreous humor
The 3 forms of Diabetic Neuropathy
1. Peripheral, Symmetric Neuropathy of the
lower extremities –> Disturbance of both motor and sensory function
2. Autonomic Neuropathy –> Disturbance of
bowel and bladder function
3. Diabetic Mononeuropathy –> Sudden footdrop, wrist-drop or isolated cranial nerve palsies
The 2 PanNETs associated with MEN-1 syndrom (mutation)
*PanNETs: Pancreatic Neuro-Endocrine Tumours
1) Insulinomas (in the pancerase)
2) Zollinger-Ellison Syndrome (Gastrinomas)
location of Insulinomas
pancrease
location of Gastrinomas (Zollinger-Ellison syn.)
Gastrinoma triangle:
* Duodenum
* Peri-Pancreatic soft tissues
* Pancreas
Clincal features of Zollinger-Ellison Syn.
1) Hypergastrinaemia –> ↑ gastric acid secretion –> peptic ulceration
2) Peptic ulcer
3) Diarrhoea (in > 50% of patients)
clinical manifesations of Insulinomas
1) Attacks of Hypoglycaemia (low blood sugar)
2) CNS manifestations
Confusion
Stupor (state of near-unconsciousness)
Loss of consciousness
Macroscopic Features:
* Small, <2cm
* Most common, solitary lesions
* Localised to the pancreas
Microscopic Findings:
* Regular cords of monotonous cells (large cells)
* Orientation to the vasculature
* Amyloid deposits in the extracellular tissue
Are the features of what type of PanNET?
Insulinoma
primary causes of Thyrotoxicoses associated w/ Hyperthyrodism
1) Diffuse toxic hyperplasia (Grave’s disease)
2) Hyper-functioning (“toxic”) multi-nodular goiter
3) Hyper-functioning (“toxic”) adenoma
4) Iodine-induced hyperthyroidism
secondary causes of Thyrotoxicoses associated w/ Hyperthyrodism
TSH-secreting pituitary adenoma (rare)
diagnostic tests for Hyperthyroidism
- increased T3/T4
- Decreased TSH (if Primary)
Measurement of radioactive iodine uptake by the
thyroid gland
* Diffusely [increased/decreased] uptake in Grave’s disease
* [Increased/decreased]uptake in a solitary nodule in toxic adenoma
* [Increased /decreased] uptake in thyroiditis
- Diffusely increased uptake in Grave’s disease
- Increaseduptake in a solitary nodule in toxic adenoma
- [decreased] uptake in thyroiditis
clinical features of Cretinism
- Impaired development of skeletal and
central nervous system - Short stature
- Coarse facial features
- Protruding tongue
clinical features of Gull disease (Myxoedema)
- Generalised apathy
- Mental sluggishness
- Cold intolerance
- Obesity
- Enlargement of the tongue
- Deepening of the voice
- Constipation
- Heart enlargement and pericardial effusions
* type of hypothyroidism
LABs of Primary vs secondary Hypothyroidism
Primary Hypothyroidism:
* Increased TSH
* Decreased serum T4
Secondary Hypothyroidism:
* Not increased TSH
* Decreased serum T4
casues of Hypothyroidism
- Primary: Intrinsic abnormality in the thyroid
- Secondary: Primary Hypothalamic or Pituitary disease
Types of Thyroiditis
Chronic Lymphocytic (or Hashimoto) Thyroiditis
Granulomatous (de Quervain) Thyroiditis
Subacute Lymphocytic Thyroiditis
Riedel (Fibrous or Invasive) Thyroiditis
Chronic Lymphocytic (Hashimoto) Thyroiditis.
Linkage to ————— gene cytotoxic
Cytotoxic T-lymphocyte-associated Ag-4
gene (CTLA4)
Microscopic Findings:
* Inflammatory infiltrates (lymphocytes, plasma cells) + Germinal centers
* Atrophic thyroid follicles, lined by Hürthle or Oxyphil cells (marked eosinophil., granular cytopl.)
features of?
Chronic Lymphocytic
(Hashimoto) Thyroiditis
CF of Hashimoto Thyroiditis
Painless, symmetric and diffuse enlargement of the thyroid
(Hashimoto) Thyroiditis is associated with?
hypothyroidism (gradual development)
complications of Chronic Lymphocytic
(Hashimoto) Thyroiditis
Increased risk for development of B-cell non -Hodgkin lymphomas, within the thyroid gland
causes of Subacute Granulomatous
(de Quervain) Thyroiditis
- Viral infection
- Inflammatory process triggered by viral infections;
commonly, history of upper respiratory tract
infection
Microscopic Findings:
* Disruption of thyroid follicles –> Extravasation of
colloid –> Polymorphonuclear infiltrate –>
Lymphocytes, plasma cells and macrophages
* Development of a granulomatous reaction with
giant cells –> Granulomatous inflammation
* Healing: Resolution of inflammation and fibrosis
Macroscopic features :
- firm gland
- Intact capsule
Features of?
SubacuteGranulomatous
(de Quervain) Thyroiditis
CF of Subacute Granulomatous
(de Quervain) Thyroiditis
- Neck pain (particularly with swallowing)
- Fever
- Malaise
- Transient Hyperthyroidism –> Transient
Hypothyroidism –> Euthyroid state
(within 6-8 weeks)
casuse of Silent or painless Thyroiditis
Autoimmune
CF of silent or painless Thyroiditis (Subacute Lymphocytic Thyroiditis)
- Painless neck mass
- Thyrotoxicosis (initially) –> Euthyroid state
(within a few months)
Macroscopic Features:
* Mild symmetric enlargement of the thyroid gland
Microscopic Findings:
* Lymphocytic infiltrates and hyperplastic germinal centers
Features of?
Subacute Lymphocytic Thyroiditis (aka silent or painless Thyroiditi)
Riedel Thyroiditis is aka?
Fibrous Thyroiditis, Invasive Thyroiditis
Riedel Thyroiditis has a Relation to a group of idiopathic systemic disorders known as —————–?
Inflammatory Fibrosclerosis
CF of Riedel Thyroiditis (Fibrous/Invasive Thyroiditis)
- Hard and fixed thyroid mass
Microscopic findings:
* Thyroid replaced by fibrous tissue and inflammatory infiltrate (plasma cells , lymphocytes, macrophages)
Features of?
Riedel Thyroiditis
