Pathology of the Endocrine system 2 Flashcards
1
Q
What is the function of the parathyroid glands?
A
Production of parathyroid hormone
2
Q
What are the functions of parathyroid hormone?
A
- Mobilisation of calcium from bone
- Enhances absorption of calcium from the small intestine
- Suppressed calcium lost in urine
3
Q
How is calcium mobilised from bone?
A
PTH indirectly stimulates osteoclasts to reabsorb bone mineral, liberating Ca into blood
4
Q
How does PTH enhance calcium absorption from the SI?
A
Indirectly; by stimulating production of the active form of vitamin D in the kidney; vitamin D induces synthesis of a Ca-binding protein in intestinal epithelial cells that facilitates efficient absorption of Ca into blood
5
Q
How does PTH supress loos of Ca in urine?
A
PTH stimulates tubular reabsorption of Ca and stimulates loss of phosphate ions in urine
6
Q
Reduced PTH release leads to?
A
Hypoparathyroidism
7
Q
What are the consequences of hyperparathyroidism?
A
Hypocalcaemia → increased neuromuscular excitability → spasms, tetany, tremors
8
Q
Name some causes of hypoparathyroidism
A
- Agenesis of parathyroid glands
- Inflammation (autoimmune parathyroiditis; dogs)
- Surgical excision (eg. with thyroidectomy)
- Tumour infiltration
- Trauma
- Vit D intoxication
- Postnatal hypocalcaemia in cattle
9
Q
Describe Postnatal hypocalcaemia in cattle
A
- Parturient paresis in dairy cattle
- Complex metabolic disease (characterised by severe hypocalcaemia and hypophosphataemia near time of parturition and initiation of lactation)
- Ca levels <50% normal (in spite of PTH↑), hardly any bone resorption
- Influenced by composition of diet
10
Q
What are the consequences of hyperparathyroidism?
A
Ca mobilisation from bone → hypercalcaemia
11
Q
Primary hyperparathyroidism is due to?
A
Hyperplasia, adenoma or carcinoma of parathyroid gland
12
Q
Secondary hyperparathyroidism is due to?
A
- Consequence of chronic renal insufficiency
- Consequence of dietary Ca/P imbalance
13
Q
Tertiary hyperparathyroidism is due ti?
A
Final stage kidney disease with non-responsive, autonomous hyperparathyroidism
14
Q
Describe Pseudohyperparathyroidism
A
- Humoral malignant hypercalcaemia
- Mainly in dogs with adenocarcinoma of the anal sac (para-anal) gland or lymphomas (release of PTH-like protein!)
15
Q
How does hyperparathyroidism appear grossly?
A
Gross lesion is of bilaterally enlarged (hyperplastic) parathyroid glands
16
Q
Describe the mechanisms of renal secondary hyperparathyroidism
A
- Reduced renal Ca resorption and phosphate secretion
- Reduced Vit D activation
- Hyperphosphataemia
- Hypocalcaemia
17
Q
What are the two main consequences of renal secondary hyperparathyroidism?
A
- Fibrous osteodystrophy
- Metastatic calcification: calcium deposited within tissues
18
Q
What is fibrous osteodystrophy?
A
Calcium is liberated from the bone to return blood calcium back to normal. Mineralised matrix of the bone is replaced by a soft collagenous connective tissue
19
Q
What are the clinical signs of fibrous osteodystrophy?
A
Bone pain (lameness), loss of teeth, deformity of maxilla and mandible
20
Q
What are the gross findings of fibrous osteodystrophy?
A
“soft”, demineralised bones [Test skull, ribs!]
21
Q
Which cells are enhanced in fibrous osteodystrophy?
A
Osteoclasts
22
Q
What is normal bone substituted by in fibrous osteodystrophy?
A
- insufficiently mineralized osteoid
- collagenous connective tissue
23
Q
Atrophy of the parathyroid glands is due to?
A
Goitre or thyroid cysts (compression)
24
Q
Secondary hyperplasia of the parathyroid glands is due to?
A
Hypocalcaemia
25
Name some primary tumours of the parathyroid glands
Chief cell adenoma, adenocarcinoma (can be hormonally active which would lead to a primary hyperparathyroidism)
26
Describe the gross appearance of a parathyroid gland adenoma
Asymmetrical lesion
One side is large and is secreting hormones
One side is small/atrophic
27
Name the 3 layers of the adrenal gland
capsule
cortex
medulla
28
Name the 3 layers of the cortex of the adrenal gland
Zona glomerulosa
Zone fasciculata
Zona reticularis
29
Name the hormone secreted by the zona glomerulosa
Mineralocorticoids (aldosterone)
30
Name the hormone secreted by the zona fasciculata
Glucocorticoids (cortisol)
31
Name the hormone secreted by the zona reticularis
Sex steroids (androgens, oestrogens, progesterone)
32
Name the hormone secreted by the adrenal medulla
Catecholamines (adrenaline and noradrenaline)
33
Describe the histology of the adrenal cortex and medulla
Zona glomerulosa – cells form distinct arches
Zona fasciculata and zona reticularis – producing steroid based hormones so we see vacuolation of the cytoplasm
Medulla – producing protein based catecholamines so cytoplasm is granular
34
What are the functions of mineralocorticoids (adrenal cortex)
Main effects on ion transport of epithelial cells:
- Lead to loss of potassium (K+) and conservation of sodium (Na+)
- Most potent: aldosterone; due to: effect on enzymatically controlled electrolyte pumps in -
a) epithelial cells of distal convoluted renal tubule (cation exchange mechanism, leading to resorption of Na from glomerular filtrate and secretion of K into lumen)
b) sweat glands
35
What are the functions of glucocorticoids (adrenal cortex)
- Concerned with intermediary metabolism of glucose
- Acute effects within 15-30 min, before compensatory effect of insulin!
- Increase glucose production -> hyperglycaemia
36
Glucocorticoids cause hyperglycaemia due to what mechanisms?
a) decrease in glucose uptake in adipose tissue, skin, fibroblasts, lymphoid tissue
b) increased glucose catabolism in these tissue and in muscle
c) increased gluconeogenesis (mainly in liver)
d) decreased lipogenesis, increased lipolysis in adipose tissue -> glycerol and free fatty acids
- increase protein catabolism
37
What are the functions of noradrenaline and adrenaline from the adrenal medulla?
- Fight or flight response with sympathetic NS
- Increased rate and force of contraction of the heart muscle
- Vasoconstriction
- Dilation of bronchioles
- Stimulation of lipolysis of fat cells
- Increased metabolic rate
- Dilation of pupils
38
Primary hypoadrenocorticism is also known as?
Addisons disease
39
Describe primary hypoadrenocorticism
- Humans, dog, cat, horse, usually idiopathic cortical atrophy
- Usually all zones of the adrenal cortex affected
- Non-specific symptoms (mineralo- and glucocorticoids affected)
40
Secondary hypoadrenocorticism is due to?
Hypopituitarism (ACTH↓)
41
Hyperadrenocorticism linked to hyperaldosteronism is due to?
Nodular hyperplasia, adenoma or carcinoma of zona glomerulosa [endocrine activity]
42
Hyperadrenocorticism linked to hyperaldosteronism has what consequnces?
Metabolic acidosis
| Oedema
43
Adrenal dependent Hypercortisolism is also known as?
Cushings syndrome
44
What are the consequences/clinical signs of Cushings syndrome?
Polydipsia, polyuria, polyphagia, obesity (trunk)
Atrophy of skeletal muscle, alopecia, epidermal atrophy
Osteopenia
Secondary diabetes mellitus
45
Describe primary adrenal Cushing syndrome
With adenoma or carcinoma of zona fasciculata
46
Describe paraneoplastic Cushing syndrome
Ectopic ACTH production in non-pituitary tumours (eg. bronchial carcinoma, thymoma, pancreatic carcinoma)
47
Describe iatrogenic Cushing syndrome
- Side effect of glucocorticoid (or ACTH) therapy
- Mainly in dogs (and cats) e.g. itchy dogs on chronic prednisolone therapy
- Will lead to negative feedback at the pituitary gland and bilateral adrenal atrophy. Sudden cessation of therapy results in hypoadrenocorticism due to atrophic glands. Don’t stop steroid therapy suddenly
48
What are some general features of hyperadrenocorticism?
- Increased appetite and food intake
- Weakened and atrophic muscles (extremities, abdomen)
- Gradual abdominal enlargement, lordosis, muscle trembling
- Atrophy of temporal muscles
- Hepatomegaly (fat and glycogen storage)
- Skin alterations
49
Describe the gross skin lesions of hyperadrenocorticism
- Progressive bilateral symmetrical alopecia
- Fine, paper thin, wrinkled texture, hyperpigmentation
- Mineralisation (calcinosis cutis)
50
Describe the histological skin lesions of hyperadrenocorticism
- Atrophy of epidermis, hair follicles and sebaceous glands
- Loss of collagen and elastin in dermis and subcutis
- Inactive hair follicles with infundibular dilatation and hyperkeratosis
- Diffuse othokeratotic hyperkeratosis
- Cutaneous mineralisation (calcinosis cutis) (deposition of mineral crystals along collagen and elastin fibres)
51
Describe circulatory disorders of the adrenal glands
- Hyperaemia with intoxications and sepsis
| - Haemorrhage in sepsis, intoxication and fatal stress
52
Adrenal cortical insufficiency is also termed?
Addisonian crisis
53
Describe adrenal cortical insufficiency
- Stress induced (circulatory, infectious, toxic, traumatic or thermal insults)
- Often with cortical necrosis
54
What causes adrenal cortical atrophy?
Prolonged glucocorticoid therpay
55
Which zone is mostly affected by adrenal cortical atrophy?
Zona fasciculata
56
Describe the effects of reduced mineralocorticoid levels in hypoadrenocorticism
- Severe hyperkalaemia, reduced serum Na and Cl
- Cardiovascular disturbances due to hyperkalaemia
- Progressive dehydration and haemoconcentration due to loss of Na
57
Describe the effects of reduced glucocorticoid levels in hypoadrenocorticism
- Moderate hypoglycaemia (due to gluconeogenesis↓ and insulin sensitivity↑)
- Hyperpigmentation of skin (due to increased MSH release)
58
Bilateral cortical hyperplasia (=secondary hyperplasia) is due to?
Persistently elevated ACTH levels - pituitary hyperplasia
59
If active cortical adenomas produce?
Cushings
60
What is a Phaeochromocytomas?
Medullary neoplasm
61
What makes up the endocrine pancreas?
Islets of Langerhans (pancreatic islands)
62
Islets of Langerhans (pancreatic islands) are composed of?
a) alpha cells [60-70%; insulin]
b) beta cells [20%; glucagon]
c) delta cells [somatostatin]
d) PP cells [pancreatic polypeptide]
e) D1 cells [vasoactive intestinal peptide]
f) enterochromaffin cells [serotonin]
63
Describe the effects of insulin on carbohydrate metabolism
- Facilitates entry of glucose into muscle, adipose and other tissues (facilitated diffusion)
- Stimulates liver to store glucose as glycogen (activation of several enzymes involved in glycogen synthesis)
- Decreases glucose concentration in blood
64
Describe the effects of insulin on lipid metabolism
- Promotes synthesis of fatty acids in the liver (when liver is saturated with glycogen, additional glucose is used for synthesis of fatty acids export as lipoproteins
- Inhibition of breakdown of fat in adipose tissue (inhibition of intracellular lipase -> further accumulation of fat)
65
How are the brain and liver not linked to glucose?
Brain and liver do NOT require insulin for efficient glucose uptake - their level of glucose is dependant on blood glucose level
66
A lack of insulin leads to?
A catabolic state
67
Describe a catabolic state due to a lack of insulin?
- Increased gluconeogenesis from glycogen and protein -> hyperglycaemia
- Reduced protein synthesis -> wasting of tissues
- Increased lipolysis, diminished uptake of free fatty acids in adipose tissue -> hyperlipidaemia
- hyperosmolarity, profound dehydration, acidosis -> neurological derangement, coma
68
What are the consequences of hyperglycaemia?
Increased glucose load in primary urine -> glycosuria, osmotic diuresis, thirst
69
What are the consequences of hyperlipidaemia?
Fatty acid metabolisation in the liver via acetyl-CoA, in absence of glucose -> ketoacids -> ketoacidosis
70
Name 3 endocrine pancreas neoplasms
a) Insulinoma (β-cell adenoma)
b) Gastrinoma [Zollinger-Ellison syndrome]
c) Glucagenoma [hyperglycaemia, Diabetes mellitus]
71
What are the consequences of insulinomas?
Hyperinsulinism, hypoglycaemia, neurological signs
72
What are the clinical signs of an insulinoma?
Seizures
Weakness, depression, lethargy
Ataxia, posterior weakness
Polyphagia, anorexia
73
Zollinger-Ellison Syndrome is seen with?
Gastrinoma
74
Describe the consequences of a gastrinoma
Secretion of gastrin -> gastric hypersecretion -> hyperacidity, mucosal hyperplasia, ulceration
75
Type 1 diabetes is ... dependant
Insulin
76
Describe type 1 diabetes causes and features
- Severe, absolute lack of insulin due to reduction of beta cell mass
- Acute onset, but based on chronic autoimmune attack of beta cells
- Lymphocyte-rich inflammatory infiltrate in islets
77
Describe primary diabetes in different animals
With extensive neoplastic destruction of pancreatic tissue
OR
In dogs: a) with acute pancreatic necrosis, chronic fibrosing pancreatitis. b) occasionally early-onset diabetes (purebred dogs) due to islet hypoplasia
- In cats: with islet amyloidosis
- In cattle: with chronic FMD
78
Describe type II diabetes?
= non-insulin-dependent DM
| Normal insulin production
79
Describe the 2 mechanisms of type II diabetes
a) Derangement in beta cell secretion of insulin
b) Decreased response of peripheral tissues to insulin [“insulin resistance”]
- Due to genetic defects of insulin receptor and insulin signalling pathways
- Due to obesity
80
Secondary diabetes mellitus occurs due to?
As a consequence or complication of other diseases
| Due to antagonism between insulin and other hormones
81
Describe some example causes of secondary diabetes mellitus
a) Endogenous progesterone (bitch): persistent corpora lutea
b) Pituitary tumours: due to growth hormone production
c) Cats, dogs: hyperadrenocorticism
82
What lesions are seen with diabetes mellitus?
- Emaciation, (dehydration)
- Hepatic lipidosis, vacuolation of bile duct epithelium [due to glycogen accumulation]
- Glycogen nephrosis
- Cataract (dogs)
