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Year 2 - Endocrinology (DP) > Pathology > Flashcards

Flashcards in Pathology Deck (144):
1

What is the basic pathophysiology of T2DM?

1. Insulin receptors become less sensitive to insulin
2. Less glucose enters cells
3. Hyperglycaemia

2

What causes insulin resistance?

Ectopic fat accumulation
Increased FFA circulation
Increased CRP
Reduced glycogen synthesis

3

How does insulin resistance affect β-cells?

Results in:
- Hyperglycaemia
- Lipotoxicity (Increased FFA + triglycerides)
These reduce β-cell function

4

What kind of obesity is associated with increased risk of T2DM and CVS disease?

Central

5

What is central obesity associated with?

Metabolic syndrome:
- High BP
- High triglycerides
- Low HDL
- Insulin resistance

6

What is the thyroid gland mainly composed of?

Follicles:
- Surrounded by flat/cuboidal epithelial cells
- Thyroglobulin in centre (amorphic and pink)
Scattered C cells:
- Parafollicular

7

What do C cells look like?

Slightly larger than follicular cells
Clearer cytoplasm

8

What function do C cells have?

Secrete calcitonin:
- Reduces serum calcium

9

What does TSH do?

1. Binds to TSH-receptor on epithelial cells
2. G-proteins activated:
- GTP -> GDP
- Production of cAMP
> Increased production/release of T3 + T4

10

What two forms do T3 and T4 circulate in?

Bound
Free

11

When T3 and T4 bind to target cell receptors, what happens?

1. Complex translocates to nucelus
2. Binds to thyroud response elements on target genes
3. Transcription increases
4. Increased basal metabolic rate

12

What is the most common cause of hyperthyroidism?

Grave's disease

13

What is the male:female ratio for Grave's disease?

10:1

14

What is the peak age range for Grave's disease?

20-40

15

What autoantibodies are present in Grave's disease?

TSH receptor
Thyroid peroxisomes
Thyroglobulin

16

What autoantibody is relatively specific in Grave's?

Anti-TSH receptor (Thyroid stimulating)

17

What autoantibody may explain hypothyroid episodes?

TSH binding inhibitor Ig

18

What is the triad of features in Grave's disease?

Hyperthyroidism with diffuse thyroid enlargement
Exophthalmos:
- Fibroblasts express TSH receptors
Pretibial myxoedema

19

What is the most common cause of hypothyroidism?

Hashimoto's Thyroiditis (Autoimmune)

20

What are some associations for Hashimoto's?

Middle aged women
Other autoimmune disease
HLA-DR3 + HLA-DR5

21

What age do people get Hashimoto's Thyroiditis?

45-60 years old

22

What has been shown in twin studies for Hashimoto's?

Autoantibodies are present in asymptomatic siblings

23

What do polymorphisms in CTLA-4 cause?

Dysregulation of T cell responses
Reduced protein level and function:
- Increased risk of autoimmune disease

24

What does PTPN-22 normaly do?

Inhibits T cell function

25

What autoantibodies are present in Hashimoto's Thyroiditis and what happens when they're bound?

Anti-Thyroglobulin and Anti-Peroxidase
When bound:
- Ab-dependent cell mediated cytotoxicity

26

What cells may mediate thyroid epithelium destruction?

CD8 positive cells

27

What is the process of cytokine mediated cell death?

IFNγ:
- Recruits macrophages -> Damages follicles

28

What is Hashitoxicosis?

When Hashimoto's Thyroiditis is preceded by transient hyperfunction

29

What does Hashimoto's predispose to?

Other autoimmune disease
B-cell non-Hodgkin's Lymphoma in affected gland

30

What is a goitre?

Any thyroid enlargement

31

In what populations is there an increased incidence of diffuse goitre?

Females
Pubescent
Young adults

32

How else can diffuse goitre arise?

Ingesting substances which reduce T3/T4 production
Dyshormonogenesis:
- Cretinism (in kids)
Mostly idiopathic

33

How does diffuse goitre usually present?

Euthyroid:
- T3/T4 normal
- TSH raised
Mass effects

34

How does a Multi-Nodular Goitre arise?

Long-standing simple goitre:
- Recurrent hyperplasia + involution
- Impressive enlargement

35

What is a differential of multi-nodular goitre?

Neoplasm

36

What is the pathogenesis of multi-nodular goitre?

Follicle rupture -> Haemorrhage -> Scarring -> Calcification

37

What mass effects can multi-nodular goitre have?

Cosmetic
Airway obstruction
Dysphagia
Vessel compression

38

How does an autonomous multi-nodular goitre present?

Hyperthyroid

39

What is the most common cause of a goitre?

Iodine deficiency:
- Lack of intake
- Lack of bioavailability

40

What type of neoplasm appears a discrete solitary mass encapsulated by a surrounding collagen cuff?

Thyroid adenoma

41

What is a thyroid adenoma difficult to distinguish from?

Dominant nodule in MNG
Follicular carcinoma

42

If a thyroid adenoma secretes thyroid hormones, is it classed as TSH-dependent or TSH-independent?

TSH-independent

43

What mutations can cause a thyroid adenoma?

RAS
PIK3CA

44

What mutations are seen in functional thyroid adenomas?

TSHR signalling pathway:
- TSHR
- G-proteins

45

What people are at greatest risk of thyroid carcinomas?

Females
Early adulthood

46

Ionising radiation predisposes to what type of thyroid cancer?

Papillary

47

Iodine deficiency predisposes to what type of thyroid cancer?

Follicular

48

What genetic features are seen in papillary cancer?

Active MAP kinase pathway:
- Rearrange RET/NTKR1
- BRAF point mutation

49

What genetic features are seen in follicular cancer?

Mutations in PI3K/AKT

50

What genetic features are seen in anaplastic cancer?

MAP kinase mutations
PI3K/AKT mutations
p53 + -catenin mutations

51

What genetic features are seen in medullary cancer?

MEN2 (Germline RET mutations)

52

What is the structure of a papillary thyroid carcinoma?

Solitary nodule:
- Can be multifocal
- Often cystic
- May be calcified

53

What worsens the prognosis of a papillary thyroid cancer?

Age >40
Extra-thyroid extension
Distant metastases

54

What is the structure of a follicular thyroid carcinoma?

Usually a single nodule:
- Enlarges slowly
- Painless
- Non-functional
May surround capsule

55

Where do medullary thyroid carcinomas arise from?

C cells:
- Neuroendocrine
- Can secrete calcitonin

56

What can medullary thyroid carcinomas be related to?

MEN2A or MEN2B:
- Often presenting in younger patients

57

How do familial medullary thyroid cancers appear?

Bilateral/Multicentric
C cell hyperplasia

58

What are medullary thyroid carcinomas composed of?

Spindle/Polygonal cells
Arranged in:
- Nests
- Trabeculae
- Follicles

59

What deposits are seen in medullary thyroid cancer?

Amyloid (abnormally folded calcitonin)

60

What effects do medullary thyroid cancers have?

Mass:
- Dysphagia
- Hoarseness
- Airway obstruction
Paraneoplastic:
- Diarrhoea (VIP production)
- Cushing's (ACTH production)

61

What is the most undifferentiated and aggressive thyroid carcinoma?

Anaplastic

62

What are the parathyroid glands composed of? What do they look like and what do they secrete?

Chief cells:
- Round
- Moderate cytoplasma
- Bland, round, central nuclei
Secrete PTH

63

What are the supporting cells in the parathyroid gland? What do they look like?

Oxyphil cells:
- Larger
- Acidophilic cytoplasm

64

What is parathyroid hyperplasia associated with?

MEN1 and MEN2A

65

How does a parathyroid adenoma appear?

Single gland -> 0.5-5grams
Other glands are atrophic
Microscopically represents normal glands
Fibrous CT capsule:
- Adjacent rim of compressed tissue

66

What happens in secondary hyperthyroidism?

Chronic hypocalcaemia:
- Results in compensatory overactivity

67

What are signs of secondary hyperthyroidism?

Renal failure
Low calcium intake
Vitamin D deficiency

68

What happens in tertiary hyperparathyroidism?

Autonomous activity
Associated with hypercalcaemia

69

What are the signs of hyperparathyroidism?

Bones
Stones (Kidney and Gallstones)
Groans (Constipation/Peptic ulcer/Pancreatitis)
Psychic overtones
CVS:
- Aortic/Mitral calcification

70

What specific bone problem can hyperparathyroidism cause?

Osteitis Fibrosa Cystica

71

What can DiGeorge syndrome cause? What is the mutation seen?

Congenital absence of thyroid and parathyroid glands:
- Hypoparathyroidism
Chromosome 22q11.2

72

What is familial hypoparathyroidism associated with?

Primary adrenal insufficiency (Addison's)
Mucocutaneous candidiasis

73

What are signs of hypoparathyroidism?

Tetany:
- Neuromuscular irritability
- Chvostek's and Trousseau's Signs
Basal ganglia calcification
Parkinsonian
Increased ICP:
- Papilloedema
Cataracts
QT prolongation

74

What is the adenohypophysis and where is it derived from?

Anterior pituitary
Derived from Rathke's Pouch

75

What is the neurohypophysis and where is it derived from?

Posterior pituitary
Extension of neural tissue:
- Modified glial cells
- Axonal processes

76

What hormones are secreted by the anterior pituitary?

Trophic:
-TSH, ACTH, FSH, LH
Non-trophic:
- GH
- PRL

77

What hormones are secreted by the posterior pituitary?

ADH
Oxytocin

78

How is the anterior pituitary composed histologically?

Acidophils:
- Somatotrophs -> GH (50%)
- Mammotrophs -> PRL (20%)
Basophils:
- Corticotrophs -> ACTH (20%)
- Thyrotrophs -> TSH (5%)
- Gonadotrophs -> FSH/LH (5%)
Chromophobe

79

Are the axons forming the posterior pituitary myelinated or not?

No

80

What can cause anterior pituitary hyperfunction?

Adenoma
Carcinoma

81

What can cause anterior pituitary hypofunction?

Surgery/Radiation
Haemorrhage (Apoplexy)
Ischaemic necrosis (Sheehan Syndrome)
Tumours extending into sella
Sarcoidosis

82

What conditions affect the posterior pituitary?

Diabetes insipidus:
- Lack of ADH secretion
SIADH:
- Ectopic secretion (tumour)
- Primary pituitary disorder

83

What percentage of intra-cranial tumours are pituitary adenomas?

10%

84

What disorder is pituitary adenoma associated with? What is this condition called?

MEN1 -> Wermer Syndrome

85

What size is a microadenoma and what size is a macroadenoma?

Micro is 1cm

86

How do we classify pituitary adenomas?

By cell type/hormone produced

87

Are all pituitary adenomas functional?

No:
- 25-30% are hypofunctional/non-functional

88

True or false; if a pituitary adenoma is functional, hormones can be secreted at a subclinical level?

True

89

What subset of pituitary adenomas are aggressive?

Those with p53 mutations and many mitotic figures

90

What can large pituitary adenomas cause?

Bitemporal hemianopia
Pressure atrophy
Infarct -> Panhypopituitarism

91

What does a PRL-secreting pituitary adenoma cause?

Infertility
Decreased libido
Amenorrhoea

92

What does a GH-secreting pituitary adenoma cause?

GH -> Increased IGF
Stimulates growth of:
- Bone
- Cartilage
- Connective tissue
Gigantism/Acromegaly

93

What does a ACTH-secreting pituitary adenoma cause?

Cushing's
Usually Micro
BAH

94

True or false; Pituitary hypofunction is usually panhypopituitarism?

True

95

What tumours can cause pituitary hypofunction?

Rathke Cleft cysts

96

What causes of granulomas can cause pituitary hypofunction?

Sarcoidosis
TB meningitis

97

How does a patient with apoplexy present?

Headache
Diplopia (CN iii pressure)
Hypopituitarism
CV collapse
Loss of consciousness

98

What hypothalamic tumours can cause pituitary hypofunction?

Benign:
- Craniopharyngioma
Malignant:
- Glioma
- Metastases

99

Where are craniopharyngiomas derived from?

Rathke's pouch

100

What are the features of craniopharyngiomas?

Slow growing
Often cystic
May calcify

101

Where do most craniopharyngiomas arise?

Suprasella

102

What ages are craniopharyngiomas most common?

Bimodal:
- 5-15 years
- 50-60 years

103

How do craniopharyngiomas present?

Headache
Visual disturbance
Reduced growth in children

104

What is central diabetes insipidus and what can cause it?

ADH deficiency
Caused by:
- Trauma
- Tumours
- Inflammation

105

What is nephrogenic diabetes insipidus?

Renal resistance to ADH

106

Where re the adrenal glands located?

Superomedial to the upper pole of the kidneys

107

What are the three zones of the adrenal cortex (from superficial to deep)? What are the functions of each?

Zona glomerulosa:
- Produces mineralocorticoids + aldosterone
Zona fasciculata:
- Produces glucocorticoids + cortisol
Zona reticularis:
- Produces sex steroids + glucocorticoids

108

What nerves innervate the adrenal medulla?

Pre-synaptic SNS fibres

109

What cells are in the adrenal medulla and what do they secrete?

Neuroendocrine/Chromaffin cells:
- Secrete catecholamines
> Adrenaline
> NA
> Small amount of dopamine

110

What other diseases can manifest in the adrenal gland?

Pituitary -> ACTH secretion
Shock/DIC
Conditions damaging gland

111

What three general pathologies can cause adrenal hyperfunction?

Hyperplasia
Adenoma
Carcinoma

112

What can cause acute and chronic adrenal hypofunction?

Acute:
- Waterhouse-Friderischsen
> Haemorrhage after Neisseria meningitidis
Chronic:
- Addison's

113

What mode of inheritance is CAH?

Autosomal recessive

114

What is the pathogenesis of CAH?

1) 21-hydroxylase deficiency
2) Reduced steroid synthesis:
- No cortisol or aldosterone production
3) Increased androgen production -> Virilisation

115

What does the decreased cortisol in CAH result in?

ACTH release
Cortical hyperplasia

116

What can cause acquired adrenal hyperplasia?

Endogenous ACTH:
- Pituitary adenoma -> Cushing's Disease
- Ectopic ACTH -> Small Cell LC
Bilateral adrenal enlargement

117

What are the types of adrenal enlargement?

Diffuse -> ACTH driven
Nodular -> ACTH-independent

118

What should you suspect if there is an adrenocortical tumour in children?

Li-Fraumeni syndrome

119

What can an adrenocortical carcinoma present with?

Fever (due to necrosis)

120

A well-circumscribed and encapsulated adrenocortico tumour. Approximately 2cm diameter, with a yellow-brown cut surface.

Adrenocortical adenoma

121

How can an adrenocortical carcinoma spread?

Locally:
- Retroperitneum
- Kidney
Vascular spread to liver, lungs and bone
Peritoneum and pleura
Regional LNs

122

What features suggest an adrenocortical carcinoma?

Large size:
- >50g
- >20cm
Haemorrhage + necrosis
Frequent and atypical mitoses
Capsular/Vascular invasion

123

What can adrenocortical adenomas resemble and how?

Cortical cells:
- Well differentiated
- Small nuceli
- Rare mitotic figures

124

What can cause a massive adrenal haemorrhage?

Newborn
Anticoagulants
Disseminated Intravascular COagulation (DIC)
Waterhouse-Friderichsen

125

What are the three common causes of chronic adrenal insufficiency?

Autoimmune destruction
Infection:
- TB
- Fungal (Histoplasma)
- HIV
Metastases (Lung and breast)

126

How much of the adrenal gland needs to be destroyed for there to be symptoms?

>90%

127

What biochemical results are seen in Addison's?

Hypoglycaemia
Hyperkalaemia
Hyponatraemia
Hypovolaemia
Hypotension

128

What can cause an Addisonian crisis?

Infection
Surgery/Trauma

129

Where do adrenal medullar neuroblastomas arise?

40% from medulla
60% along sympathetic chain

130

What is the general composition of a medullar neuroblastoma?

Primitive cells
May show maturation to ganglion cells

131

What features worsen the prognosis of a adrenal medulla neuroblastoma?

N-myc amplification
Telomerase expression

132

What cells is a phaeochromocytoma derived from?

Chromaffin cells in the adrenal medulla

133

What can a phaeochromocytoma cause?

Paroxysmal secondary hypertension:
- Stress/Exercise/Posture/Tumour palpation
- Micturition

134

Which of the following is not a complication of phaeochromocytomas:
- CHF
- MI
- CVA
- PAD
- Arrhythmia

PAD

135

How is phaeochromocytoma diagnosed biochemically?

Urinary:
- Catecholamines
- Metabolites

136

Phaeochromocytomas are the 10% tumour. What does this mean?

10% are extra-adrenal:
- Paragangliomas
- Organs of Zuckerkandl
- Carotid body
10% are bilateral
10% are malignant
10% are NOT associated with hypertension

137

What percentage of Phaeochromocytomas are familial? What are features of familial Phaeochromocytomas?

25%:
- Germline mutations
- Younger and bilateral
- 30% malignant if β-subunit of succinate dehydrogenase mutation

138

What features of a phaeochromocytoma suggest it is malignant?

Large
Necrotic

139

How do phaeochromocytomas appear?

Yellow and red-brown
BUT can vary up to
Haemorrhagic and necrotic

140

What makes phaeochromocytomas appear brown?

K2Cr2O7:
- Oxidises catecholamines

141

What do tumour cells in a phaeochromocytoma form?

Nests (Zellballen)

142

What syndrome are phaeochromocytomas a feature of?

MEN2A -> Sipple Syndrome
and also MEN2B

143

What causes MEN2A and what are they at risk of?

RET oncogene germline mutations -> 10q11.2
They have:
- Phaeochromocytomas
- Medullary thyroid cancer
- PTH hyperplasia

144

What causes MEN2B and what are they at risk of?

RET point mutations
They have:
- Phaeochromocytomas
- Medullar thyroid cancer
- Neuromas
- Ganglioneuromas
- Marfanoid habitus