Endocrine Path Flashcards
1
Q
The endocrine system consists of [] that maintain body homeostasis. They fxn by releasing [] that travel via [] to distant organs.
A
- Group of glands
- Hormones
- Blood
2
Q
What are 2 subtypes of pituitary adenoma? What differentiates them?
A
- Functional: Tumor produces hormone
- Non-Functional: Tumor is silent and does not produce hormone
3
Q
How do non-hormone secreting pituitary adenomas cause clinical symptoms?
A
Nonfunctional tumors often present with mass effect (where the tumor’s growth/size physically impairs the surrounding tissues)
4
Q
What are some clinical symptoms due to mass effect of pituitary adenomas? Why does each occur?
A
Mass effect is often seen in non-fxnal tumors; 3 assoc. symptoms due to mass effect are:
- Bitemporal hemianopsia (due to compression of optic chiasm)
- Hypopituitarism (due to compression of normal pituitary tissue)
- Headache (due to compression of brain tissue)
5
Q
What is the most common type of functional pituitary adenoma?
A
Prolactinoma
6
Q
How does prolactinoma present in females? In males?
A
- In females, prolactinoma presents as galactorrhea and amenorrhea
- In males, prolactinoma presents as decreased libido and headache
7
Q
What is the treatment for prolactinoma? Give 2 examples.
A
- Dopamine agonists (b/c DA has inibitory regulation of prolactin in the body)
- Bromocriptine or Cabergoline
8
Q
Which pituitary adenoma is associated with gigantism in children and acromegaly in adults?
A
Growth Hormone Cell Adenoma
9
Q
What symptoms do growth hormone cell adenoma cause in children? In adults?
A
Children: Increased linear bone growth (since
Adults: Acromegaly (enlarged bones of hands, feet, and jaw; growth of visceral organs; enlarged tongue)
10
Q
What are the clinical features of acromegaly? What is the most common cause of death in these patients?
A
- Enlarged bones of hands, feet, and jaw; Growth of visceral organs; enlarged tongue
- Growth of visceral organs leads to dysfxn (e.g. cardiac failure, which is the most common cause of death in these Pts)
11
Q
What comorbidity is often seen in Pts w/ growth hormone cell adenoma? Why does this happen?
A
- Secondary diabetes mellitus
- GH induces liver gluconeogenesis and also decreases glucose uptake into the cell = increases blood glucose levels
12
Q
How is growth hormone cell adenoma diagnosed?
A
Pt’s GH and insulin-like growth factor-1 (IGF-1) levels will be elevated & oral glucose suppression test would show Pt’s GH is unaffected by glucose consumption
13
Q
What are the available treatments for growth hormone cell adenoma? What is the MoA by which the pharmacologic treatment modalities works?
A
- Octreotide (a somatostatin analog) or GH receptor antagonist or surgery
Octreotide: somatostatin (octreotide) blocks release of GHRH by the hypothalamus –> Ant. pituitary is not stimulated to release GH
GH Receptor Antagonist: prevents GH from binding to its receptor on tissues
14
Q
What kind of clinical condition is associated with ACTH cell adenomas?
A
Cushing Syndrome
15
Q
When do symptoms of hypopituitarism arise?
A
When >75% of pituitary parenchyma is lost
16
Q
What are 3 causes of hypopituitarism?
A
- Pituitary adenomas (adults) or Craniopharyngioma (children)
- Sheehan Syndrome
- Empty Sella Syndrome
17
Q
What is the MoA by which pituitary adenomas and craniopharygniomas cause hypopituitarism?
A
Due to mass effect (and physical compression/destruction of the gland) or pituitary apoplexy (where hemorrhage into the adenoma causes rapid increase in size and compression/destruction of the gland)
18
Q
What is the MoA by which Sheehan syndrome causes hypopituitarism?
A
During prego, pituitary gland doubles in size, but blood supply doesn’t increase in proportion –> gland becomes susceptible to infarction especially if there is a lot of blood loss during parturition
19
Q
What are observable clinical symptoms associated with Sheehan Syndrome?
A
Poor lactation (due to low prolactin); loss of pubic hair* (HY: since pubic hair is dependent on androgens); Fatigue (partly due to decreased TSH production)
20
Q
What is the MoA by which Empty Sella Syndrome causes hypopituitarism?
A
Empty Sella Syndrome is a congenital defect of the sella, where Pt becomes predisposed to have herniation of the arachnoid and CSF into the sella –> compression/destruction of pituitary gland
21
Q
What are the 2 hormones secreted by the Posterior Pituitary? Where are they produced?
A
- ADH and oxytocin
- ADH and oxytocin are made in the hypothalamus –> travel to Post. Pit. via axons for release
22
Q
What is the fxn of ADH and Oxytocin?
A
- ADH: Act on DCT and CD of kidney to promote free-water retention (concentrate the urine)
- Oxytocin: Mediate uterine contraction during labor + release of breast milk in lactating mothers
23
Q
What disease would be caused by a deficiency of ADH?
A
Central Diabetes Insipidus
24
Q
What are the symptoms of Central Diabetes Insipidus?
A
Clinical feats are based on loss of free-water
- Polyuria and polydipsia w/ life-threatening dehydration
- Hypernatremia and high serum osmolality (due to ECF contraction)
- Low urine osmolality and specific gravity (due to inability to concentrate the urine)
25
What would be seen in a water deprivation test in a normal Pt as opposed to a Pt w/ Central Diabetes Insipidus?
- Normally, after Pt is deprived of water, urine osmolality should increase as the person releases ADH to retian more water
- In a Pt w/ CDI, Pt would show no/insufficient increase in urine osmolality
26
What is the treatment for Central Diabetes Insipidus?
Desmopressin (ADH analog)
## Footnote
*- Since the Pt's problem is a deficiency and not due to receptor defects*
27
What disease is caused by an impaired renal response to ADH?
Nephrogenic Diabetes Insipidus
28
What are 2 drugs that can cause nephrogenic diabetes insipidus?
1. Li+
2. Demeclocycline
29
How could you differentiate b/w Central Diabetes Insipidus and Nephrogenic Diabetes Insipidus?
Clinically, both are very similar. However, NDI would not respond to desmopressin
30
What disease is associated with excessive ADH secretion?
Syndrome of Inappropriate ADH (SIADH)
31
What is the most common cause of SIADH?
Ectopic production (e.g. small cell carcinoma)
32
What alkalating drug can cause SIADH?
Cyclophosphamide
33
What symptoms can be seen in SIADH?
SIADH clinical feats are based on the excessive free water retention
- Hyponatremia and low serum osmolality (due to ECF expansion)
- Mental status changes and seizures (due to osmolar gradient produced by the hyponatremia causing water to enter the neuronal cells of the brain [cerebral edema])
34
What is the treatment for SIADH?
Free-water restriction or demeclocycline
35
How do thyroglossal duct cysts develop?
Embryologically, thyroid develops @ base of tongue --\> travels along thyroglossal duct to the ant. neck
- Normally, thyroglossal duct should involute and close off, but if it persists, it may undergo cystic dilation
36
How can you differentiate a thyroglossal duct cyst from a lingual thyroid based on observation?
Thyroglossal duct cysts would present as as an ant. neck mass, while lingual thryoid would present as a mass @ base of tongue
37
How does one develop a lingual thyroid?
Lingual thyroid is if the thyroid tissue does not travel down the thyroglossal duct in embryological devo and persists @ base of tongue
38
What are the 2 main causes underlying all the clinical symptoms seen in hyperthyroidism?
1. Increased basal metabolic rate (due to increased Na/K ATPase --\> increased demand for ATP --\> increased gluicose/fat mobilization)
2. Increased SANS activity (Thyroid hormone increases expression of B1-adrenergic receptors)
39
What is the lipid & glucose profile of a Pt w/ hyperthyroidism? Why does this happen?
- Hypocholesterolemia (TH increases LDL receptor gene expression; increases LPL & hepatic lipase activity; increases CETP transfer of cholesterol from HDL to VLDL)
- Hyperglycemia (TH stimulates gluconeogenesis & glycogenolysis)
40
What is Graves Disease (be specific)?
Type II Hypersensitivity disease where Pt makes a stimulatory IgG Ab against TSH receptor on Thyroid gland
41
What is the most common cause of hyperthyroidism?
Graves Disease
42
What are 4 clinical symptoms of Graves Disease? Explain how/why each occurs.
1. Hyperthyroidism (stimulatory Abs are produced that stimulate TSH receptor --\> increase synythesis & release of TH)
2. Diffuse goiter (constant TSH receptor stimulation leads to thyroid hyperplasia and hypertrophy)
3 & 4. Exopthalmos and Pretibial myxedema (Fibroblasts behind the eye and overlying the shin have TSH receptors --\> stimulatory Abs make these fibroblasts secrete excess glycosaminoglycans)
43
What is the cause for Exopthalmos and Pretibial myxedema seen in Graves Disease?
Fibroblasts behind the eye and overlying the shin have TSH receptors --\> stimulatory Abs make these fibroblasts secrete excess glycosaminoglycans (chondroitin sulfate + hyaluronic acid) --\> inflammation + fibrosis
44
What histologic changes to the follicular structure is seen in Graves Disease?
Scalloping of colloid (normally, colloid should be bordering the follicle epithelium; but in Graves disease, you will see some jagged white b/w the colloid and follicle epith)
45
Explain the laboratory findings you'd find in a Pt w/ Graves Disease (Total and free T4, TSH, Cholesterol, and Serum Glucose)
- Total and free T4: increase (due to stimulatory Abs)
- Decreased TSH (since free T4 downregulates TRH receptors on ant. pit via neg fb --\> decreased TSH production)
- Hypocholesterolemia (due to increased cholesterol uptake facilitated by TH)
- Increased serum glucose (TH stimulates gluconeogenesis + glycogenolysis)
46
What are the treatment modalities for Graves Disease?
- Beta-blockers (to decrease SANS response to TH)
- Thioamides (to block critical fxns of peroxidase in the TH synthesis pthwy)
- Radioiodine ablation (Follicles would take up the radioactive iodide and be destroyed)
47
What is a thyroid storm? What can precipitate this condn?
- Thyroid storm is a potentially fatal complication of Graves Disease, which presents as arrhythmia, hyperthermia, and vomiting + hypovolemic shock
- Usually occurs due to elevated catecholamines and massive hormone excess, often in response to stress (e.g. surgery or childbirth)
48
What are the treatment modalities for thyroid storm?
PTU (propylthiouracil; type of thioamide so it can block peroxidase involved in TH synthesis, but it can also inhibit deiodase in the periphery that converts T4 into T3); Beta-blockers; Steroids
49
What kind of goiter is seen in Pts w/ relative iodine deficiency?
Multinodular goiter
50
What kind of hormonal issues are usually seen in multinodular goiter? What is a rare complication?
- Multinodular goiters are usually nontoxic (euthyroid; no hormonal excess or deficiency)
- Rarely, regions of the multinodular goiter may become TSH-independent and begin releasing T4 w/o TSH stimulation (toxic goiter) --\> causes hyperthyroidism
51
What condition does hypothyroidism cause in neonates and infants?
Cretinism
52
What are clinical symptoms that characterize cretinism? (5)
1. Mental retardation
2. Short stature w/ skeletal abnormalities
3. Coarse facial feats
4. Enlarged tongue
5. Umbilical hernia
53
Why is thyroid hormone crucial to the devo of a neonate?
TH is required for normal brain and skeletal devo
54
What are 4 common causes for cretinism in a neonate/infant?
1. Maternal hypothyroidism during early prego
2. Thyroid agenesis
3. Dyshormonogenetic goiter (congential defect in TH production; most commonly b/c the thyroid gland has a dysfxnal peroxidase)
4. Iodine deficiency
55
What is most commonly the reason for cretinism symptoms if the underlying cause is due to dyshormonogenetic goiter?
Due to dysfxnal thyroid peroxidase of the thyroid gland in the fetus
56
Hypothyroidism in older children or adults presents as what condition?
Myxedema
57
Myxedema due to hypothyroidism presents w/ a myriad of clinical features. What is the underlying cause that all these symptoms share?
The clinical features are based on decreased BMR and decreased SANS due to the hypothroidism
58
When hypothyroidism occurs in older children and adults, there may be a deepening of voice and enlargement of tongue. What is this process caused by?
There is compensatory increase in TSH by Ant. Pit. in myxedema due to hypothyroidism --\> Fibroblasts via stimulation of TSH secrete GAGs --\> GAGs accumulate in the skin and soft tissue --\> results in deepening of voice if it accumulates in larynx and glossomegaly if it accumulates in tongue
59
Why do patients w/ myxedema due to hypothyroidism become short of breath and become fatigued easily?
TH stimulates B1-adrenergic receptors --\> Bradycardia + decrease CO --\> hypoxia --\> shortness of breath
60
What are the most common causes of hypothyroidism in older children and adults?
Iodine deficiency and Hashimoto thyroiditis
61
What is Hashimoto Thyroiditis (be specific)?
Autoimmune destruction of thyroid gland (type IV HSR)
62
What surface marker receptor is associated with Hashimoto Thyroiditis?
HLA-DR5
63
Why could you see a transient hyperthyroidism in the early stages of Hashimoto Thyroiditis?
Due to autoimmune destruction of follicles, some T3 and T4 may leak out --\> hyperthyroidism
64
Once Hashimoto Thyroiditis progresses to hypothyroidism, what changes to T4 and TSH levels would be seen in the Pt?
T4 would decrease (due to destruction of follicles) and TSH would increase (due to decrease T4 = decrease neg. fb to Ant. Pit --\> increase TSH release)
65
What serum markers can be seen in Hashimoto Thyroiditis that signify thyroid damage?
Antithyroglobulin and antithyroid peroxidase Abs (since these leaked out from the follicles during the destruction)
66
What are 3 histologic findings seen in Hashimoto Thyroiditis?
1. Chronic inflammation
2. Germinal centers
3. Hurthle cells (eosinophilic metaplasia of cells that line the follicle)
67
Hurthle cells are a characteristic histological finding in what disease?
Hashimoto Thyroiditis
68
Pts w/ Hashimoto Thyroiditis have an increased risk for what cancer?
B-cell (marginal zone) lymphoma (recall marignal zone arises from post-germinal center B-cells; in Hashimotos, you get increased stimulation of germinal centers due to chronic inflammation --\> marginal zone lymphoma)
69
What clinical presentation of a Pt w/ Hashimoto Thyroiditis would warrant concern of the Pt developing a secondary cancer?
Enlarging thyroid gland late in disease course
70
Subacute granulomatous (de quervain) thyroiditis presents with what clinical findings?
Tender thyroid w/ transient hyperthyroidism
71
What usually precipitates subacute granulomatous de quarvain thyroiditis?
Viral infxn
72
What is the prognosis of Subacute granulomatous de quervain thyroiditis? What complication may arise?
- SGDQT is self-limited
- Rarely, it can progress to hypothyroidism
73
How does riedel fibrosing thyroiditis clinically manifest?
Hypothyroidism w/ "hard as wood" non-tender thyroid gland
74
What is the cause for the clinical findings seen in riedel fibrosing thyroiditis?
Chronic inflammation w/ extensive fibrosis of thyroid gland
75
Why is airway obstruction a concern in Riedel Fibrosing Thyroiditis?
There is extensive fibrosis of the thyroid gland in RFT --\> fibrosis may extend to involve local structures (e.g. airway)
76
Riedel fibrosing thyroiditis clinically mimics what other thyroid disease? How can it be differentiated from the other?
- Anaplastic carcinoma
- Riedel patients are typically younger (40s), while anaplastic carcinoma are seen in elderly. In addition, malignant cells would be absent in Riedels upon biopsy.
77
Are thyroid nodules more likely to be benign or malignant?
Benign
78
Why are I-131 radioactive uptake studies useful in diagnosing thyroid cancer?
It can further characterize nodules:
- Increased uptake ("hot" nodule) is seen in Graves disease nad nodular goiter
- Decreased uptake ("cold" nodule) is seen in adenoma and carcinoma
79
What I-131 radioactive uptake result is associated with thyroid cancer? What would be the next immediate step?
- Decreased uptake ("cold" nodule)
- If decreased uptake is seen, biopsy should be taken to further characterize the nodule
80
Why would you avoid normal biopsy technique when taking a sample from the thyroid? What kind of biopsy should you do?
- Thyroid is a highly vascularized tissue; if you use normal biopsy technique, it would bleed excessively
- Use fine needle aspiration (FNA) for thyroid biopsy
81
What are the 4 types of thyroid carcinomas?
1. Papillary Carcinoma
2. Follicular Carcinoma
3. Medullary Carcinoma
4. Anaplastic Carcinoma
82
What kind of thyroid nodule is characterized by benign proliferation of follicles surrounded by fibrous capsule?
Follicular adenoma
83
What is the metabolic activity of a follicular adenoma?
Usually nonfxnal; less commonly, it may secrete thyroid hormone
84
What is the most common type of thyroid carcinoma?
Papillary carcinoma (~80% of cases)
85
What is a major risk factor in developing papillary carcinoma?
Ionizing radiation in childhood (e.g. Child who received radiation for severe acne on face - this used to be a treatment modality long time ago)
86
What are 3 characteristic histological findings in papillary carcinoma?
1. Papillae (often assoc w/ psammoma bodies)
2. Orphan Annie eye nuclei (you see a white,clear space in center of nucleus)
3. Nuclear grooves (you see a small line w/n the nucleus in some of the cells)
87
Where do papillary carcinoma of thyroid often spread to? What is the prognosis of this disease?
- Cervical lymph node
- Excellent prognosis, even if it spreads (10yr survival \> 95%)
88
How do you differentiate follicular carcinoma of thyroid from folicular adenoma by gross exam?
Both follicular carcinoma and follicular adenoma would have proliferation of follicles surrounded by a fibrous capsule. However, if examined grossly, follicular addenoma would have invasion through the capsule.
89
Why is FNA insufficient to differentiate b/w follicular carcinoma and follicular adenoma? What would you have to do to differentiate?
- FNA only examines the cells and not the capsule; you'd see proliferating follicles in both diseases
- Enire capsule would have to be examined microscopically to see if there is invasion (carcinoma) or if there is not (adenoma)
90
By what route does follicular carcinoma metastasize?
Follicular carcinoma metastasizes hematogenously (*this is in contrast from general rule that carcinomas metastasize via lymph*)
91
What are 4 carcinomas that deviate from the general rule of spreading via lymph node, and rather spread hematogenously?
1. Renal Cell Carcinoma
2. Hepatocellular Carcinoma
3. Follicular Carcinoma
4. Choriocarcinoma
92
Which thyroid cancer is due to a malignant proliferation of parafollicular C cells?
Medullary carcinoma
93
What hormone do Parafollicular C cells normally produce? What is the fxn of this hormone?
- Calcitonin
- Calcitonin is responsible for lowering serum Ca2+ (increasing renal Ca2+ excretion + increasing Ca2+ absorption by bone)
94
What changes to a Pt's serum Ca2+ could be seen in medullary carcinoma of thyroid?
Hypocalcemia due to high levels of calcitonin being produced by tumor
95
What kind of amyloidosis could be seen in medullary carcinoma? What is it caused by?
Localized amyloidosis due to calcitonin depositing w/n the tumor
96
What would biopsy reveal in medullary carcinoma of thyroid?
Aggregates of malignant cells in an amyloid stroma (*the amyloid will appear very eosinophilic - almost looks like follicles, but it'd be in much more irregular shape + no follicular epith cells*)
97
If a Pt develops medullary carcinoma of thyroid due to a heritable condition, what is this condition called? What oncogene mutation is this associated with?
- Multiple endocrine neoplasia (MEN) 2A and 2B
- *RET* oncogene mutation
98
What tumors are associated with MEN2A? MEN2B?
- MEN2A: Medullary carcinoma, pheochromocytoma, and parathryroid adenomas
- MEN2B: Medullary carcinoma, pheochromocytoma, and ganglioneuromas of oral mucosa
99
If *RET* mutation is detected, what procedure may the Pt elect to undergo?
*RET* mutations are assoc w/ MEN2A and 2B, both of which increase the risk of medullary carcinoma of thyroid; Pt may elect to undergo prophylactic thyroidectomy
100
What is anaplastic carcinoma of the thyroid? What patient group is usually affected?
- Undifferentiated malignant tumor of the thyroid
- Usually seen in elderly
101
What does anaplastic carcinoma of thyroid clinically mimic? What is the prognosis of this condn?
- Anaplastic carcinoma of thyroid usually mimics Riedel's fibrosing thyroiditis, since it often invades local structures --\> can cause dysphagia or respiratory compromise
- Poor prognosis
102
What is the key fxnal cell in the parathyroid gland? What do they secrete/how is it regulated?
Chief cells - secrete PTH in response to decreased serum free (ionized, not bound to protein or phosphate) Ca2+
103
What is the MoA by which PTH increases serum free Ca2+?
1. Increases bone osteoclast activity by stimulating osteoblasts to secrete RANK-L --\> releases Ca2+ and phosphate
2. Increases small bowel absorption of Ca2+ and phosphate by activating Vitamin D (PTH increases activity of 1-alpha-hydroxylase)
3. Increases renal Ca2+ reabsorption (DCT) and decreases phosphate reabsorption (PCT)
104
What is primary hyperparathyroidism? What is secondary hyperparathyroidism?
- Primary hyperparathyroidism: excess PTH due to disorder of the parathyroid gland itself
- Secondary hyperparathyroidism: excess PTH due to a disease process not directly involving parathyroid gland
105
What is the most common cause of primary hyperparathyroidism? What are 2 other less common causes?
- Parathyroid adenoma (\>80% of cases)
- Other less common causes are: sporadic parathyroid hyperplasia and parathyroid carcinoma
106
How many of the 4 glands does parathyroid adenoma usually involve?
One
107
What is the most common clinical outcome of parathyroid adenoma? What are 5 possible complications that may arise (kidney, CNS, GI, Bone)?
- Most commonly, parathyroid adenoma is assoc w/ asymptomatic hypercalcemia
- Complications may arise, however, but are all assoc w/ the increased PTH and hypercalcemia:
1. Nephrolithiasis (calcium oxalate stone due to increase Ca2+ filtration)
2. Nephrocalcinosis (metastatic calcification of renal tubules)
3. CNS disturbances (e.g. depression and seizures)
4. Constipation, peptic ulcer disease, and acute pancreatitis
5. Osteitis fibrosa cystica (resorption of bone leading to fibrosis and cystic spaces
108
How could parathyroid adenoma cause acute pancreatitis?
Parathyroid adenoma would increase serum Ca2+ --\> Ca2+ is an activator of enzymes --\> Ca2+ may activate the digestive enzymes w/n the pancreas to cause dmg/inflammation
109
What lab findings would be expected in a Pt w/ parathyroid adenoma? (Serum PTH, Serum Ca2+, Serum Phosphate, Urinary cAMP, Serum Alkaline Phosphate)
- Increase in serum PTH
- Increase in serum Ca2+
- Decrease in serum Phosphate
- Increase in urinary cAMP (PTH receptor is a Gs-CPR)
- Increase in serum alkaline phosphatase (sign of osteoblast activity; PTH stimualtes osteoblasts which then in turn activates osteoclasts)
110
What is the most common cause of secondary hyperparathyroidism?
Chronic renal failure
111
What is the MoA by which chronic renal failure may cause secondary hyperparathyroidism?
Chronic renal failure causes renal insufficiency (inability of kidney to properly fxn) --\> decreased phosphate excretion --\> increased phosphate binding w/ serum free Ca2+ --\> Decrease in serum free Ca2+ --\> All 4 parathyroid glands become stimulated to secrete more PTH --\> Increased PTH causes bone resorption --\> renal osteodystrophy
112
What lab findings would be expected in secondary hyperparathyroidism? (PTH, serum Ca2+, serum phosphate, and alkaline phosphatase)
- Increase in PTH
- Decrease serum Ca2+
- Increase serum phosphate
- Increase alkaline phosphatase
113
What genetic syndrome is associated with hypoparathyroidism?
DiGeorge Syndrome (failure to devo 3rd & 4th pharygneal pouch, of which parathyroid develops from)
114
What clinical findings would be seen in hypoparathyroidism related to muscle? Why does this happen?
- Muscle spasms (tetany) would be observed in hypoparthyroidism due to the low serum calcium
- After muscle excitation, Ca2+ is excreted from the cell due to NCX, which is an antiporter that brings in 3 Na+ for 1 Ca2+ --\> there is an increased gradient for Ca2+ to leave the cell due to hypocalcemia, but due to the positive net charge entering the cell, the muscle cell becomes more readily excitable
115
What are two physical tests that can be done to induce muscle spasm in Pts w/ hypoparathyroidism?
- Trousseau sign (filling a BP cuff induces muscle spasm)
- Chvostek sign (tapping on facial nerve induces muscle spasm)
116
What lab values would be expected in hypoparathyroidism? (PTH and serum Ca2+)
- Decrease in PTH
- Decrease in Ca2+
117
What is pseudohypoparathyroidism? What may be a reason for this condn?
- Hypoparathyroid symptoms arise due to end-organ resistance to PTH (not a problem with the parathyroid gland itself)
- May be due to a congenital defect of the Gs-CPR (PTH receptor) found on that target tissue (Autosomal Dominant)
118
What lab values would be expected in pseudohypoparathyroidism? (PTH and serum Ca2+)
- Increase PTH (due to compensatory rxn)
- Decrease Ca2+ (since defective PTH receptor)
119
If pseudohypoparathyroidism is caused by a genetic defect, what clinical manifestations can be expected to be seen on the patient?
Short stature & short 4th/5th digits
120
What cluster of cells encompasses the endocrine pancreas? Are they homogeneous?
- Islets of Langerhans
- No, a single islet consists of multiple cell types, each produce one type of hormone
121
What cell type secretes insulin? Where are they located, specifically?
- Beta cells of the pancrease secrete insulin
- Beta cells lie in the center of the islets of langerhans
122
What type of receptors does insuline upregulate in skeletal muscle and adipose tissue?
Insulin-dependent glucose transporters (GLUT4)
123
What anabolic mechanisms are upregulated by the increased glucose uptake in skeletal and adipose tissues?
Glycogen synthesis, protein synthesis, and lipogenesis
## Footnote
*(essentially all storage mechanisms; you're mobilizing the glucose)*
124
What cells secrete glucagon? What is the major purpose of this hormone and how does it accomplish it?
- alpha cells in the Islet of Langerhan of the pancreas secrete glucagon
- Glucagon's role is to oppose insulin (which decreases serum glucose by increasing uptake) and increase blood glucose levels via glycogenolysis and lipolysis
125
What is the pathophysiology of Type I DM that causes hyperglycemia seen in this disease?
Insulin deficiency due to autoimmune (Type IV HSR) destruction of beta cell by T lymphocytes
126
What changes in the islets of langerhans would be observed in type I DM?
Inflammation of the islets would be observed due to the T lymphocyte-mediated destruction
127
What MHC receptor genes are associated with Type I DM?
HLA-DR3 and HLA-DR4
128
When does Type I DM present in patients?
Manifests in childhood
129
What is the high serum glucose in Type I DM caused by?
Autoimmune destruction of Beta cells = Lack of insulin --\> decreased glucose uptake by fat and skeletal muscle
Also, unopposed glucagon causes gluconeogenesis --\> exacerbates hyperglycemia
130
Why do patients with Type I DM present with weight loss, low muscle mass, and polyphagia?
- Due to lack of insulin, Pt has unopposed glucagon --\> increase in gluconeogenesis glycogenolysis and lipolysis (catabolic rxns); but Pt still has difficulty in glucose uptake = loss of weight and low muscle mass (b/c Pt is breaking down muscle for AA for gluconeogenesis)
- Pt may eat a lot as a compensatory rxn b/c body is trying to get more fuel for these catabolic rxns
131
What is the pathophysiological cause of polyuria, polydipsia, and glycosuria seen in Type I DM?
Hyperglycemia (due to increased gluconeogenesis and lack of insulin) exceeds renal ability to resorb glucose --\> excess is filtered and goes down through the tubules --\> leads to osmotic diuresis (since glucose is an osmotically active substance)
132
What is the treatment for Type I DM?
Lifelong insulin
133
Which type of DM is at risk for developing diabetic ketoacidosis? What is this complication characterized by?
- Type I DM
- Diabetic ketoacidosis is characterized by excessive serum ketones
134
What usually precipitates a Pt w/ Type I DM to develop diabetic ketoacidosis? Why is this the case?
- Diabetic Ketoacidosis often arises w/ stress (e.g. infxn)
- Epinephrine stimulates glucagon secretion --\> further exacerbates lipolysis --\> increased lipolysis causes increased free fatty acids --\> Liver converts FFAs to ketone bodies (beta-hydroxybutyric acid and acetoacetic acid)
135
What serum glucose level would be expected in Type I DM?
\> 300 mg/dL
136
Explain how anion gap metabolic acidosis and hyperkalemia develop in Type I DM.
- Anion gap metabolic acidosis is due to the ketoacids in serum (*side note: anion gap is the difference b/w + charges and - charges in blood*)
- Hyperkalemia in Type I DM is caused by 2 reasons:
* Insulin drives K+ into cells
* One buffering mech of body to counter acidosis is to bring H+ into cells in exchange for K+
137
Why is the hyperkalemia seen in Type I DM misleading as to the actual state in the body?
Although K+ may be high in the blood, overall, the Pt is losing K+ since insulin is absent (therefore decreased K+ reabsorption by cells) & since increased H+/K+ antiporter (mechanism to counter acidosis) --\> more K+ is being excreted in their urine
138
What respiratory changes are seen in Pts w/ diabetic ketoacidosis?
Kussmaul respirations (rapid breathing w/o dyspnea) to try to induce resp. alkalosis to counter the ketoacidosis
139
What is the cause of fruity smelling breath seen in Type I DM?
Increase in acetone being produced due to ketoacidosis
140
What is involved in the treatment of diabetic ketoacidosis?
Fluids (to correct dehydration from polyuria), insulin, and electrolyte replacement (esp. potassium)
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What is the pathophysiological cause of hyperglycemia seen in Type II DM?
Hyperglycemia in Type II DM is due to insulin resistance by target organs
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What is the most common type of DM?
Type II DM is the most common type of diabetes (90% of cases)
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What type of patients are affected by type II DM? What makes this patient population more susceptible to type II DM?
- Middle-aged, obese adults
- Obesity leads to decreased # and sensitivity of insulin receptors; there is also a strong genetic predisposition for developing Type II DM
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What is the MoA that makes Type II DM patients need insulin later on in the disease course?
Early in disease, insulin levels are increased, but later, insulin deficiency develops due to Beta cell exhaustion
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Histology would show what changes in the islets of Langerhans in Type II DM?
Amyloid deposition (after exhaustion of Beta cells)
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What is the normal range of glucose levels? How is diagnosis of Type II DM made using glucose levels? (Random glucose, fasting glucose, glucose tolerance test)
- Normal glucose levels should be: 70 - 120 mg/dL
- In Type II DM:
* Random glucose: \> 200 mg/dL
* Fasting glucose: \> 126 mg/dL
* Glucose tolerance test (bolus of glucose is given to Pt) w/ serum glucose level \> 200 mg/dL 2 hours after glucose loading
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What is the first line of treatment that is recommended for Type II DM?
Diet and exercise for weight loss in order to sensitize the insulin receptors
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What is a dangerous complication that can arise from Type II DM? What is this condn characterized by?
Hyperosmolar non-ketotic coma: If Pt w/ Type II DM develops high hyperglycemia (\> 500 mg/dL), this may lead to life-threatening diuresis w/ hypotension and coma
## Footnote
*It is non-ketotic since ketone bodies are absent since some insulin is still able to circulate and oppose the glucagon effects*
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