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Pathology > Endocrinology > Flashcards

Endocrinology Flashcards

1
Q

Define diabetes and explain the genetic defects present in type 1 diabetes

A

Defective or deficient insulin secretory response leading to impaired glucose use

T1 and T2 diabetes

Genetic defects in B-cell function caused by defects on chromosomes 2, 7 or 12 as well as mitochrondrial DNA

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2
Q

What things cause secondary diabetes

A
  • Chronic pancreatitis (damage to islets of lagerhands that produce insulin)
  • Haemochromatosis- increased iron deposits in pancreas and liver cause damage
  • Infections- rebella or CMV
  • Adrenal or pituitary tumours
  • Drugs (steroids, pentamidine)
  • Genetic disorders- Downs syndrome
  • Gestational diabetes mellitus- pregnancy
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3
Q

Describe the pathogenesis in type 1 diabetes

A
  • Onset under 20
  • Decreased blood insulin
  • Anti-islet cell antibodies
  • Ketoacidosis is common
  • HLA-D linked
  • Autoimmune reaction related
  • Severe insulin deficiency
  • Inflammation of islet cells causes atrophy and fibrosis leading to beta cell depletion
  • Northern europeans
  • Usually patients will have islet cell autoantibodies or other autoimmune diseases eg RA
  • Can be linked to measles, rubella and coxsackie B
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4
Q

Describe the pathogenesis of type 2 diabetes

A
  • Onset over 30
  • Linked to obesity
  • Normal or increased blood insulin
  • Family linked
  • Caused by insulin resistance
  • No inflammation of islet cells but mild depletion in Beta cells
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5
Q

How does insulin stimulate the uptake of glucose into cells

A
  1. Insulin attaches to the insulin receptor on a cell membrane
  2. Once attached this leads to an increased production of glucose transport units to allow more glucose into cells and this increases protein and DNA synthesis
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6
Q

Discuss the changes in the pancreas caused by type 1 diabetes

A
  • Reduction in number and size of islets
  • Leukocytic inflammation of islets- insulitis
  • Causes beta cell degranulation
  • Reduction in islet cell mass
  • Amyloid deposition in pancreas
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7
Q

How is the vascular system affected by diabetes and explain why they occur

A

Causes accelerated atherosclerosis leading to MI or gangrene in the extremities
-Relates to how well diabetes is controlled

It is due to

  • elevated blood lipids or low levels of HDL
  • Increased thromboxane A2 activity (increases platelet stickiness so increases risk of thrombosis)
  • Causes hyaline arterioles
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8
Q

What are the renal complications associated with diabetes

A
  • Large vessel disease - renal artery narrowing causes renal ischaemia and HTN
  • Diabetic microangiopathy- involvement of small kidney vessels
    - Diffuse thickening of the basement membrane (uniform thickening due to glucogenated collagen proteins)
    - glomerular lesions - Diffuse and nodular glomerulosclerosis
    - Vascular lesions - hyaline arteriosclerosis (narrowed afferent and efferent arterioles as hyaline replaces the muscles in media)
    - Pyelonephritis (increased infection risk) and papillary necrosis- usually seen in diabetes- necrosis of papilla due to ischaemia- it sloughs off and goes into the ureter , can cause obstruction
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9
Q

Describe the ocular complications associated with diabetes

A
  • Microangiopathy
  • Visual impairment
  • Blindeness
  • Retinopathy
  • Cataract formation
  • glaucoma
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10
Q

Describe the neurological complications of diabetes

A
  • Peripheral symmetrical neuropathy involving sensory motor or autonomic nerves
  • Microangiopathy in the CNS can lead to cerebral haemorrhage and then cerebral infarction

-Neuropathy is due to paralysation of small blood vessels that inadequates supply nerves thus leading to muscle damage

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11
Q

Describe the skin complications associated with diabetes

A
  • Recurrent infections
  • Necrobiosis lipodica diabeticorum
  • Granuloma annulare
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12
Q

What are the pregnancy complications associated with diabetes

A
  • Pre-eclamptic toxaemia
  • Large immature babies
  • Neonatal hypoglycaemia
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13
Q

describe the normal histology and physiology of the thyroid

A
  • Thyroid follicular epithelium makes up thyroid follicles they store thyroid hormone in colloid
  • TSH released by pituitary acts on thyroid causing release of T3 and T4 which reversibly bind to thyroxine binding globulin
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14
Q

What are the causes of hyperthyroidism

A
  • Diffuse hyperplasia of thyroid gland
  • Ingestion of exogenous hormone
  • Hyperfunction goitre
  • Thyroiditis
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15
Q

What are some disorders that are associated with hyperthyroidism

A
  • Diffuse toxic hyperplasia (Graves disease)
  • Toxic multi nodular goitre
  • Toxic adenoma
  • Acute/ subacute thyroiditis
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16
Q

What are the clinical features of hyperthyroidism

A

Overactivity of sympathetic nervous system

  • Cardiac manifestations -tachy palpitations, arrhythmias, congestive HF
  • Osteoporosis
  • Tremour , hyperactivity, emotional, anxiety
  • Warm sweaty skin
  • Increased appetite, weight loss , increased bowel mobility
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17
Q

What investigations are needed for a Hyperthyroidism diagnosis

A

Free T4 increased and low TSH usually
TSH level after TRH injection
-Radioactive iodine uptake by thyroid= indicating factor of activity in gland
-TSH levels usually decreased or low

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18
Q

What are the causes of hypothyroidism

A
  • Insufficient thyroid tissue due to underdeveloped, radiation injury or hashimotos thyroiditis
  • Interference with thyroid hormone synthesis- drugs, idodine deficiency, idiopathic primary hypothyroidism
  • Suprathyroidal- pituitary lesions reducing TSH secretion, hypothalamic lesions
19
Q

What are the features of hypothyroidism in infancy

A
  • Endemic in iodine deficient areas
  • Poor development of skeleton and CNS - severe mental retardation
  • T3/T4 cross veto/materal barrier before birth
20
Q

Discuss the features of adult hypothyroidism

A
  • Myxoedema
  • Decreased sweating
  • Constipation
  • Accumulation of matrix substances in subcutaneous tissue
  • Slow physical and mental activity
  • Fatigue, sluggishness
  • Speech
  • Cold intolerant, weight gain
  • SOB and low exercise tolerance
21
Q

What are the investigation findings in Hypothyroidism

A

-Decreased T3 T4 and elevated TSH

22
Q

Name the various types of thyroiditis

A

-Hasimoto’s - symmetrical atrophy, lymphoid infiltrates replace normal thyroid follicles, eosinophilic cytoplasm- most common cause of thyroiditis, caused by defect in T cells that involves cellular and humeral immunity, more common in females 45-65 , painless thyroid enlargement

-Graves - Hyperthryoid due to hyper functional diffuse enlargement, exopthalmos and pretibial myxoedema, genetic features HLA B8 and DR3 , TSH receptor antibodies bind to TSH receptor and stimulate thyroid hormone production (mimic TSH) - Increased T3 and T4, TSH decreased - can mimic a carcinoma with tightly packed follicles histologically 
Both autoimmune
-Granulomatous 
-Subcut lymphocytic 
Palpation (post surgery)
23
Q

Describe the features of a thyroid adenoma

A
  • Benign
  • Solitary mass in a normal thyroid gland with an intact surrounding capsule (no invasion of capsule as benign)
  • Difficult to differentiate from follicular cancer
  • No vascular invasion
24
Q

What are the 4 types of malignant carcinomas of the thyroid

A
  • Papillary carcinoma- most common
  • Follicular carcinoma
  • Medullary carciona
  • Anaplastic carcinoma
25
Q

Discuss the features of a papillary carcinoma

A
  • Differentiated (cells look like they are from the thyroid
  • Most common
  • 20-40 yrs
  • Thyroid nodules
  • Imaging and Fine need asp for diagnosis
  • Good survival
  • Well formed vascular papillae lined with neoplastic cells
  • The nucleus has enlarged nuclei and wrinkled cell membrane
26
Q

Discuss the features of follicular carcinoma

A
  • Differentiated
  • Follicular pattern with capsule +/- vascular invasion
  • Spreads through blood to lung and bone
  • Minimally invasive
  • Has to have invaded capsule/ vascular to be a follicular carcinoma*
27
Q

Discuss the features of a medullary carcinoma

A
  • Neuroendocrine tumour from parafollicular C cells
  • Can secrete calcitonin (check this in blood tests)
  • Associated with MEN 2A and 2B syndromes
  • Can produce stroll amyloid
  • Can met
28
Q

Discuss the features of an anapaestic carcinoma

A
  • Undifferentiated, pleomorphic (don’t look like cells from thyroid)
  • High mortality- invades neck structures
  • Rare
  • Around 65 mean age
  • High mitotic rate
29
Q

Discuss the features of a poorly differentiated carcinoma

A
  • In between differentiated thyroid cancer and an undifferentiated anaplastic cancer
  • Widely invasive with necrosis and vascular invasion
  • Poor survival
30
Q

Discuss the features of a thyroid lymphoma

A

Rare
Can cause thyroiditis/ make it worse
Usually B cell and low grade

31
Q

What is a carcinoid tumour

A
  • Can present in many organs but most commonly seen in GI tract
  • Occur at any age but usually between 50-60
  • 50% small intestine tumours 2% colorectal tumours
  • They make many products and hormones eg insulin, calcitonin and 5HT
  • Potentially malignant- more aggressive when in stomach or small intestine
32
Q

Describe the features of carcinoid syndrome

A
  • GI carcinoids rarely produce symptoms but some can cause Z-E syndrome due to production on gastrin (gastric ulcer)
  • Syndrome is seen in patients with metastatic carcinoid or in patients with elevated 5HT and 5HIAA due to tumour

Features of syndrome

  • Skin flushing and cyanosis
  • Diarrhoea , cramps , nausea, vomiting
  • Cough, wheeze, dyspnoea
  • Hepatomegaly (mets)
  • Cardiac involvement
33
Q

Describe the 4 types of Cushings syndrome (the 4 causes of the syndrome)

A
  1. Pituitary cushing syndrome - Tumour producing ACTH increases cortisol release from the adrenal gland
  2. Adrenal Cushing syndrome - Hyperplasia of the adrenal gland causing increased cortisol release
  3. Paraneoplastic bushings syndrome- Lung tumour or other neuroendocrine cancer producing ACTH causing increased cortisol release from adrenal gland
  4. Iatrogenic Cushing syndrome- use of steroids
34
Q

What are the features of Cushing’s syndrome

A
  • Central obesity
  • Moon facies
  • Weakness and fatigue
  • HTN
  • Increased hair
  • Diabetes
  • Osteoporosis
  • Neuropsychiatric abnormalities
  • Skin striae
35
Q

What are the main causes of primary adrenal insufficiency

A
  • under functioning adrenal gland*
  • Loss of cortex
  • Idiopathic
  • Infection
  • AIDS
  • Acute haemorrhage necrosis
  • Amyloidosis , sarcoidosis , haemochromatosis
  • Metastatic carcinoma
36
Q

Describe the features of Secondary adrenal Insufficiency

A
  • usuall
  • over functioning pituitary gland*
  • Hypothalamic pituitary disease
  • Neoplasm, inflam, sarcoid
  • Hypothalamic pituitary suppression
  • Long standing steroids
37
Q

What are the features of an adrenal cortical adenoma

A
  • Occurs in the cortex
  • Yellow in colour
  • Encapsulated and have adrenocortical cells
38
Q

What are the features of an adrenal carcinoma

A
  • In the cortex
  • Rare
  • Malignant
  • Tumour replaces adrenal gland and invades capsule
39
Q

What are the features of a phaeochromocytoma

A
  • From the adrenal medulla
  • From sympathetic nervous system cells
  • Produces excess catecholamines
  • Causes fight or flight symptoms
  • Can be malignant
  • Genetic link - MEN
  • Tanned colour with rim of normal adrenocortex
40
Q

Name some of the most common pituitary adenomas

A
  • Prolactin cell adenoma (most common)
  • Growth hormone cell adenoma
  • ACTH cell adenoma
  • Gonadotroph cell adenoma
  • These will all put pressure of the optic nerve (they sit in optic chasm) and will cause bitemporal hemianopia
  • Adults 30-50
  • Usually always benign
  • Clinical symptoms relate to the hormone its producing
  • Associated with genetic MEN1
41
Q

Discuss the pathological types of adenoma and what they secrete

A

Acidophil adenoma- secretes growth hormone in excess
Basophil adenoma - ACTH excess
Chromophobe adenoma- no hormone effect/ can produce prolactin
Microadenoma- prolactin can cause infertility

42
Q

What are the clinical features of pituitary tumours

A
  • Endocrine abnormality + effect of mass lesion
  • Pressure on optic chiasm - bitem portal hemianopia
  • Increased ICP due to expanding mass in brain- head nausea vomiting
43
Q

Discuss the features and causes of hypopituitarism

A

Causes

  • Tumours/ other mass lesions
  • Pituitary surgery/ radiation
  • Pituitary haemorrhage
  • Ischaemic necrosis
  • Genetic
  • Associated with metastatic carcinoma

Pathology (12 decks)

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