Endocrine Pathology From Robbins/lecture Week 2

Front 1

Normal parathyroid histology:

Back 1

Normal parathyroid gland with admixed fat.

Front 2

What type of cells are parathyroid glands mostly composed of?

Back 2

Chief cells; these cells vary from light to dark pink and contain secretory granules of PTH.

Front 3

How is the secretion of PTH from the parathyroid glands controlled?

Back 3

The activity of the parathyroids is controlled by the level of free calcium in the blood rather than by trophic hormones secreted by the pituitary or hypothalamus.

Front 4

Decreased levels of free calcium in the blood would increase or decrease PTH secretion?

Back 4

Increase

Front 5

What are the actions of parathyroid hormone?

Back 5

1. Activate osteoclasts, thereby mobilizing calcium from bone.
2. Increase the renal tubular reabsorption of calcium.
3. Increase the conversion of vitamin D to its active form in the kidneys.
4. Increases urinary phosphate excretion.
5. Augment GI calcium absorption.

Front 6

What is the difference between primary and secondary/tertiary hyperparathyroidism?

Back 6

Primary hyperparathyroidism results from spontaneous overproduction of PTH.
Secondary and tertiary hyperparathyroidism are a result of chronic renal insufficiency.

Front 7

What are the three underlying causes of hyperparathyroidism and how common are each of them?

Back 7

1. Adenoma (75-80%)
2. Primary hyperplasia (10-15%)
3. Parathyroid carcinoma (less than 5%)

Front 8

What is familial hypocalciuric hypercalcemia?

Back 8

A rare disorder caused by mutations in the calcium sensing receptor gene (CASR) on parathyroid cells leading to constant PTH secretion.

Front 9

What two mutations are common in parathyroid tumors?

Back 9

PRAD1 and MEN1

Front 10

Parathyroid adenoma histology:

Back 10

Parathyroid adenomas are composed mostly of chief cells. A rim of compressed, non-neoplastic parathyroid tissue, generally separated by a fibrous capsule, is often visible at the edge of the adenoma. In contrast to the normal parathyroid parenchyma, adipose tissue is inconspicuous within the adenoma.

Front 11

Are parathyroid adenomas usually multi-glandular or confined to a single gland?

Back 11

Confined to a single gland.

Front 12

Is parathyroid hyperplasia usually multi-glandular or confined to a single gland?

Back 12

Usually a multiglandular process.

Front 13

Parathyroid hyperplasia histology:

Back 13

Chief cell hyperplasia with a decrease in stromal fat.

Front 14

Parathyroid carcinoma histology:

Back 14

Usually firm or hard tumors occuring in one gland. Usually larger than adenomas.

Front 15

What are some of the clinical features of primary hyperparathyroidism?

Back 15

1. Increased serum ionized calcium.
2. Inappropriately increased or decreased PTH (depending on cause)
3. Hypophosphatemia
4. Bone fractures
5. Renal stones
6. GI disturbances
7. CNS alterations and neuromuscular abnormalities
8. Polyuria and polydipsia

Front 16

How does chronic renal failure cause secondary hyperparathyroidism?

Back 16

Chronic renal failure leads to decreased phosphate excretion --> hyperphosphatemia.
Elevated serum phosphate depresses serum calcium levels and lead to increased PTH secretion.
Renal failure also reduces the kidney's ability to activate vitamin D --> decreased GI absorption of calcium.

Front 17

What are some clinical features of secondary hyperparathyroidism?

Back 17

1. Bone abnormalities are less severe than that in primary hyperparathyroidism.
2. Serum calcium remains near normal b/c a compensatory increase in PTH sustain serum calcium.
3. Parathyroid glands are hyperplastic.

Front 18

Hypoparathyroidism causes:

Back 18

Much less common than hyperparathyroidism.

1. Surgical ablation
2. Congenital absence (usually in conjunction with thymic aplasia and cardiac defects in DiGeorge syndrome)
3. Autoimmune hypoparathyroidism (a hereditary polyglandular deficiency syndrome)

Front 19

Clinical features of hypoparathyroidism?

Back 19

1. Increased neuromuscular irritability.
2. Cardiac arrhythmias
3. Increased intracranial pressure and seizures.
4. Cataracts and dental abnormalities.

Front 20

BMI calculation formulas:

Back 20

Either weight in Kg / height in meters squared OR

weight in lbs * 703 / height in inches squared

Front 21

A BMI of _____ or over is considered obese?

Back 21

30

Front 22

A BMI of _____ to ______ is considered overweight?

Back 22

25 to 30

Front 23

What does the OB gene code for?

Back 23

Leptin; a protein that decreases food intake and increases energy expenditure.

Front 24

Mutations in POMC can cause obesity via failure to produce waht neuropeptide that inhibits appetite?

Back 24

alpha-MSH

Front 25

This enzyme in fat cells can convert inactive cortisone to cortisol:

Back 25

11B-hydroxysteroid dehydrogenase

Front 26

What are the four pancreatic hormones and what cells do they come from?

Back 26

1. B cells: insulin
2. A cells: glucagon
3. D cells: somatostatin; suppresses both insulin and glucagon release
4. PP cells: vasoactive intestinal peptide; stimulates secretion of gastric and intestinal enzymes and inhibition of intestinal motility.

Front 27

Normal blood glucose level is?

Back 27

Between 70 - 120 mg/dL

Front 28

The diganosis of diabetes is established by elevation of blood glucose by any one of 3 criteria:

Back 28

1. A random blood glucose level of 200 or higher, with classical signs and symptoms
2. A fasting glucose concentration of 126 or higher on more than one occasion.
3. An abnormal oral glucose tolerance test in which the glucose level is 200 or above 2 hours after a standard dose of 75mg of glucose.

Front 29

What serum fasting glucose levels or oral glucose tolerance test levels would be considered "impaired glucose tolerance"?

Back 29

111-125 for fasting serum levels.
141-199 for OGTT levels.

Front 30

Type I diabetes:

Back 30

Characterized by an absolute deficiency of insulin secretion caused by pancreatic B-cell destruction, usually resulting from an autoimmune attack. Type 1 diabetes accounts for about 10% of all cases.

Front 31

Type II diabetes:

Back 31

Caused by a combination of peripheral resistance to insulin action and an inadequate compensatory response of insulin secretion by the pancreatic B-cells. About 80-90% of all cases of diabetes are type II

Front 32

Long-term organ complications in diabetes include?

Back 32

1. Kidneys
2. Eyes
3. Nerves
4. Blood vessels

Front 33

The primary metabolic function of insulin is what?

Back 33

To increase the rate of glucose transport into certain cells in the body; the striated muscle cells (including myocardial cells) and to a lesser extent, adipocytes.

Front 34

Several mechanisms may contribute to B-cell destruction in type I diabetes:

Back 34

1. Th1 and cytotoxic T cell damage due to reaction against B-cell antigens
2. Locally produced cytokines damage B-cells
3. Autoantibodies to B-cell antigens

Front 35

A person has a greatly increased susceptibility to diabetes type I with these Type II MCH genes:

Back 35

HLA-DR3 and HLA-DR4

HLA- DR2 actually has a protective effect.

Front 36

Genetic factors play more of a role in which type of diabetes?

Back 36

Type II

Front 37

The two metabolic defects that characterize type 2 diabetes are?

Back 37

1. A decreased ability of peripheral tissues to respond to insulin
2. B-cell dysfunction that is manifested as inadequate insulin secretion in the face of insulin resistance and hyperglycemia.

Front 38

There is what type of relationship between free fatty acids and insulin in the blood?

Back 38

An inverse relationship

Front 39

What effects does thiazolidinedione have on PPARg in adipose cells?

Back 39

TZD targets the PPAR receptor in adipose cells: PPAR activation by TZD results in changes in production of adipocytokines and a lowering of FFA's in the blood.
This results in a decrease in insulin resistance.

Front 40

What is monogenic diabetes?

Back 40

A diabetic pheontype occuring secondary to loss-of-function mutations within a single gene.

Front 41

Name the three major metabolic pathways that contribute to the complications of diabetes?

Back 41

1. Non-enzymatic glycosylation
2. Activation of protein C

Front 42

Name the three major metabolic pathways that contribute to the complications of diabetes?

Back 42

1. Non-enzymatic glycosylation
2. Activation of protein C

Front 43

Name the 3 major metabolic pathways that contribute to the complications of diabetes:

Back 43

1. Non-enzymatic glycosylation
2. Activation of protein C
3. Intracellular hyperglycemia with disturbances in polyol pathways.

Front 44

How does non-enzymatic glycosylation cause problems in diabetes?

Back 44

Through the formation of "advanced glycosylation end products"; these accumulate in the interstitial tissue and blood vessel walls. This process may trap LDL in vessel walls, enhancing cholesterol deposition in the intima, accelerating atherosclerosis.
Albumin will bind to glycosylated kidney proteins --> thickening of the basement membrane.
AGE receptors on macrophages and other cells contribute to increased inflammatory and procoagulant activity.

Front 45

How does activation of protein kinase C occur in diabetes?

Back 45

Intracellular hyperglycemia induces de novo synthesis of DAG --> activation of PKC.
PKC activation may cause neovascularization of the retina (diabetc retinopathy) and increased deposition of extracellular matrix and basement membrane material.

Front 46

How does a disturbance in the polyol pathway in cause damage to nerves, kidneys, lens and blood vessels in diabetes?

Back 46

Increased use of the polyol producing aldose reductase pathway in these tissues reduces antioxidant reserves leaving them vulnerable to damage.

Front 47

Characterization of Type I diabetes from Robbins:

Back 47

An autoimmune disease characterized by progressive destruction of islet B-cells, leading to an absolute insulin deficiency. Several immune mechanisms probably contribute to B-cell damage, including cytokines, T cells, and autoantibodies.

Front 48

Characterization of Type II diabetes from Robbins:

Back 48

Has no autoimmune basis. Instead, features central to its pathogenesis are insulin resistance and B-cell dysfunction, resulting in relative insulin deficiency.

Front 49

Obesity relationship with Type II DM from Robbins:

Back 49

Obesity has an important relationship with insulin resistance, probably mediated by cytokines released from adipose tissues (adipocytokines). Other players in the adipo-insulin axis include free fatty acids and the PPARg receptor which modulates adipocytokine levels.

Front 50

Structures most likely to be damaged in even well controlled type I or II DM:

Back 50

1. Arteries
2. Basement membranes of small vessels
3. Kidneys
4. Retinas
5. Nerves

Front 51

Pancreatic cellular changes in type I DM:

Back 51

Reduction in the number and size of islets.
Leukocytic infiltration of the islets.

Front 52

Pancreatic cellular changes in type Ii DM:

Back 52

A subtle reduction in islet cell mass.
Amyloid replacement of islets in long standing disease; fibrosis may also occur.

Front 53

Diabetic macrovascular disease:

Back 53

A hallmark is accelerated atherosclerosis affecting the aorta and large and medium sized arteries.
Greater severity and earlier onset in diabetics.
Contributes to most common cause of death in diabetics; MI.
Contributes to gangrene of the lower extremities; also more common in diabetics.

Front 54

Diabetic microangiopathy:

Back 54

Diffuse thickening of basement membranes in capillaries of skin, skeletal muscle, retina, renal glomeruli and renal medulla as well as renal tubules, Bowman capsule and peripheral nerves.
Thickening is due to collagen type IV deposition in the basal lamina.
Despite the increase in the thickness of basement membranes, diabetic capillaries are more leaky than normal to plasma proteins.

Front 55

Which disease is the second most common cause of death in diabetics?

Back 55

Renal failure

Front 56

Diabetic nephropathy:

Back 56

Three types of damage are found in this disease:
1. Glomerular lesions
2. Renal vascular lesions
3. Pyelonephritis

Front 57

Types of glomerular lesions found in diabetes:

Back 57

1. Capillary basement membrane thickening.
2. Diffuse mesangial sclerosis.
- A diffuse increase in mesangial matrix and mesangial cell proliferation.
- When disease is advanced; patients manifest nephrotic syndrome - proteinuria, hypoalbuminemia and edema.
3. Nodular glomerulosclerosis.
- A ball-like lesion situated in the periphery of the glomerulus. Always associated with diabetes. Can induce sufficient ischemia to cause scarring of the kidneys.

Front 58

What type of acute pyelonephritis is more common in diabetics?

Back 58

Necrotizing papillitis (papillary necrosis)

Front 59

Ocular complications of diabetes:

Back 59

May take the form of retinopathy, cataract formation or glaucoma.

Nonproliferative retinopathy:
- characterized by capillary thickening and hemorrhage; may see small red dots.

Proliferative retinopathy:
- Will see fibrosis and neovascularization with possible retinal detachment.

Front 60

Diabetic neuropathy:

Back 60

Characterized by a peripheral, symmetric neuropathy of both motor and sensory function in the lower extremities.
May also cause disturbances in bowel, bladder, and sexual function.
Damage is caused by microangiopathy of the vessels supplying the nerves and by direct axonal damage due to alterations in polyol metabolism.

Front 61

What makes up the "classic triad" of diabetes?

Back 61

Polyuria, polydipsia and polyphagia.

Front 62

How and why are ketone bodies produced?

Back 62

Insulin deficiency leads to activation of hormone sensitive lipase, with resultant excessive breakdown of adipose stores, giving rise to increased levels of FFA's, oxidation of which by the liver produces ketone bodies.

Front 63

Type I and II DM comparison table:

Back 63

Front 64

How does production of ketone bodies lead to ketoacidosis?

Back 64

The rate at which ketone bodies are formed may exceed the rate at which they can be used, leading to ketonuria and ketonemia. If the urinary excretion of ketones is compromised by dehydration, the plasma hydrogen ion concentration increases, resulting in metabolic ketoacidosis.

Front 65

What is hyperosmolar nonketotic coma and in what population does this develop?

Back 65

Elderly type II diabetics who cannot drink enough water to compensate for the water loss from osmotic diuresis may develop this - basically severe dehydration leading to coma.

Front 66

What are the 3 top causes of mortality in both Type I and II diabetics?

Back 66

1. MI
2. Renal vascular insufficiency
3. Cerebrovascular accidents

Front 67

What is the earliest manifestation of diabetic nephropathy?

Back 67

Microalbuminuria; small amounts of albumin in the urine.

Front 68

Diagram of how ketoacidosis develops:

Back 68

Front 69

What are the 6 important organs in calcium homeostasis?

Back 69

Bone, Liver, Kidney, GI, Parathyroid and Skin
(BLK-GPS)

Front 70

Levels of calcitonin are useful for detecting what?

Back 70

Medullary carcinoma of the thyroid.

Front 71

Vitamin D levels:

Back 71

Front 72

Vitamin D effects:

Back 72

Front 73

What type of bone is the axial skeleton made of? The peripheral bones?

Back 73

Axial skeleton is made mostly of trabecular bone. The peripheral bones are made mostly of cortical bone.

Front 74

What effect does PTH have on phosphate levels?

Back 74

1. PTH increases bone resorption leading to an increase in serum calcium AND phosphate.
2. PTH inhibits renal phosphate reabsorption in the proximal tubule and increases calcium reabsorption in the distal tubule - leading to decreased serum phosphate levels.

Front 75

Cycle of hypercalcemia and dehydration:

Back 75

Front 76

What is the mnemonic for hyperparathyroid symptoms?

Back 76

Stones, bones, abdominal groans and psychic moans.

Front 77

Signs and symptoms of hyperparathyroidism:

Back 77

Front 78

Under the influence of PTH, where is most bone resorbed?

Back 78

From the surface of cortical bones.

Front 79

Which type of bone benefits most from calcium supplementation in a patient with osteoporosis?

Back 79

Trabecular bone

Front 80

Guidelines for surgical intervention in hyperparathyroidism:

Back 80

Front 81

Monitoring guidelines for silent hyperparathyroidism:

Back 81

Front 82

Signs and symptoms of hypoparathyroidism:

Back 82

Front 83

A carpal spasm induced by compression of the ulnar nerve or occlusion of the circulation is called _________ sign and is indicative of what?

Back 83

Trousseau's sign; indicative of hypocalcemia.

Front 84

Hyperactivity of the facial nerve when tapped is called _________ sign and is indicative of what?

Back 84

Chvostek's sign; indicative of hypocalcemia.

Front 85

Short stature and shortened 4th and 5th fingers are a sign of what hereditary disease?

Back 85

Pseudohypoparathyroidism

Front 86

What is the pathophysiology of psuedohypoparathyroidism?

Back 86

This disease is the result of a defective Gs protein in kidney and bone which causes end organ resistance to PTH.
- Hypocalcemia and hyperphosphatemia occur and are not corrected with administration of PTH.
- Endogenous PTH levels are elevated.

Front 87

How much calcium of the total in the body is not in the bone?

How much of that is free calcium?

Back 87

1%

1/2

Front 88

Calcium and phosphate are complexed together in the form of ___________ crystals:

Back 88

Hydroxyapatite

Front 89

What is the effect of pH on calcium serum levels?

Back 89

Hydrogen competes with calcium for binding sites on albumin.

- In an acidosis, there are more hydrogen ions --> more hydrogen ions attached to albumin and more free calcium --> increased calcemia

- In alkalosis, there is less hydrogen ions to compete with calcium, so more calcium is bound to albumin --> decreased free calcium and lowered calcemia.

Front 90

What serum calcium levels would you probably see in an acidosis? An alkalosis?

Back 90

Acidosis = hypercalcemia

Alkalosis = hypocalcemia

Front 91

What are the 3 types of cells contained in the parathyroid gland?

Back 91

1. Chief cells
2. Oxyphil cells
3. Clear cells

Front 92

What else other than low calcium can stimulate the parathyroid gland to produce PTH?

Back 92

Hyperphosphatemia

Front 93

How are chief cells stimulated to produce PTH?

Back 93

Parathyroid cells contain Ca level sensing receptors.

If extra cellular levels of Ca are high, Ca binds to receptors, activates phospholipase C which inhibits PTH production.

If Ca level is low, there is less receptor binding, serves as a stimulant for PTH secretion.

Front 94

Other conditions associated with hypercalcemia:

Back 94

Hyperparathyroidism
Malignancy (Breast, lung)
Multiple Myeloma
Osteoporosis
Sarcoidosis
Lab error
Prolonged immobilization
Prolonged ischemia
Thiazide diuretics
Vit A overdose

Front 95

What is PTHrP and what is it a marker for?

Back 95

Parathyroid Hormone related Protein; a marker for solid tumors.
Produces the same effect as PTH on bone and kidney and causes disease like primary hyperparathyroidism.

Front 96

Hypercalcemia in multiple myeloma occurs why?

Back 96

Occurs by upregulation of RANKL which activates osteoclasts (osteclast activating factor)

Front 97

Excess of what vitamin can cause activation of osteoclasts?

Back 97

Vitamin A

Front 98

Besides the Chvostek and Trousseau signs, what are some other manifestations of hypocalcemia?

Back 98

Confusion, seizures,
Weakness, cramping, spasms
Prolonged Q T, CHF
Laryngospasm, stridor

Front 99

In humans, calcitonin has little effect on regulating calcium - so what is measuring it good for?

Back 99

As a tumor marker:
(best way to diagnose) Medullary carcinoma of the thyroid, a malignant tumor of C cells (parafollicular cells)

Front 100

What is metabolic syndrome?

Back 100

Having metabolic syndrome means you have three or more disorders related to your metabolism at the same time, including:
Obesity, particularly around your waist (having an "apple shape")
SBP>120 mmHg or a diastolic BP> 80 mm Hg
An elevated level of triglycerides and a low level of high-density lipoprotein (HDL) cholesterol
Resistance to insulin

Front 101

What role in obesity does the melanocortin 4 receptor play?

Back 101

MC4R mutation accounts for 5% of individuals with childhood onset obesity. The actions of melanocyte-stimulating hormone on the melanocortin 4 receptor (MC4R) lead to a decrease in food intake, and mice with null mutations in MC4R have increased food intake, obesity, and hyperinsulinemia.
Binge eating is the common path phenotype for these mutations.

Front 102

MSH comes from a primary POMC transcript and leptin to some degree regulates POMC production - what would the effect of low leptin be?

Back 102

POMC is regulated in part by leptin. Loss-of-function mutations in POMC gene lead to obesity in mice and humans.
Leptin and leptin receptor mutations have been identified in a few families
Homozygotes: severe early obesity and hyperphagia
Heterozygotes: low leptin and high weight and can be treated with injectable leptin

Front 103

Dopamine helps regulate feeding patterns:

Back 103

Obese have lower levels of the post-synaptic dopamine D2R receptor, associated with an allele called Taq I A. Noted in 20% of obese young women.
Consistent with finding that binge eaters have low dopamine metabolite concentrations in the CSF.
Dopamine agonists are anorexigenic in the clinical situation.

Front 104

High levels of dopamine can also induce feeding through stimulation of pleasure centers.:

Back 104

Dopaminergic reward pathways provide the pleasure drive for eating as well as the rewards associated with cocaine, alcohol and nicotine.

Front 105

What are endocannabinoids and what role do they play in weight regulation?

Back 105

Endogenous lipids that bind to cannabinoid receptors 1 and 2 (CB1, CB2)
CB1 receptors are in hypothalamus, adipose and gi tract tissue
Stimulation of CB1 leads to increased oral intake and blockade leads to weight loss
CB1 receptors are expressed in the known hedonic centers (nucleus accumbens, hippocampus, and entopeduncular nucleus)

Front 106

What part of the hypothalamus integrates signals concerning satiety and hunger?

Back 106

The arcuate nucleus.

Front 107

Hunger/Satiety signals and their MOA'a:

Back 107

Front 108

What is leptin?

Back 108

Leptin is a product of the ob gene in adipocytes… an “adipokyne”
It is the molecular signal of energy abundance
Serum concentrations of leptin and circulating mRNA are in proportion to body fat mass
A decrease in leptin results in a strong hunger signal and obesity, hyperphagia, infertility, and impaired T-cell–mediated immunity in mice and humans
Administration of leptin completely reverses all aspects of the phenotype in both species.
Plays a role in the Prader-Willi syndrome.

Front 109

How does leptin work?

Back 109

Leptin drives ANOREXIA by:
Blocking NPY/AgRP axis by directly decreasing release of these molecules.
Activating POMC/CART axis via gene transcription.

Front 110

Foregut signals for hunger/satiety:

Back 110

Front 111

What is Ghrelin?

Back 111

Signals energy insufficiency.
Secreted from endocrine cells of the stomach fundus.
Preprandial rise and postprandial decline in circulating levels.
Fasting causes persistent elevations.
Prader-Willi patients (voracious hyperphagia) have elevated ghrelin levels.

Front 112

Resistin contributes to insulin resistance and DM Type II:

Back 112

Front 113

Deaths from what 2 types of cancers are increased in obese men?
3 in women?

Back 113

Men: Liver and pancrease
Women: Uterus, kidney and cervix

Front 114

Criteria for diagnosing diabetes according to Dr. Davey:

Back 114

Hemoglobin A1c ≥ 6.5%* using quality lab testing
OR Fasting Plasma Glucose (FPG) ≥ 126 mg/dl. *
OR Two hour plasma glucose ≥ 200 mg/dl during an Oral Glucose Tolerance Test (OGTT).*
OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dl.
*In the absence of unequivocal hyperglycemia, criteria 1-3 should be confirmed by repeat testing

Front 115

What are the criteria for testing for diabetes in asymptomatic individuals?

Back 115

Testing should be considered in all adults who are overweight and have additional risk factors:
First-degree relatives with diabetes
Physical inactivity
Members of high risk ethnic population (Latino, Native American)
Women having delivered a baby weighing > 9lb or had GDM
Hypertension (≥ 140/90mmHg or on antihypertensive therapy)
HDL cholesterol <35 mg/dl or triglycerides >250 mg/dl
Women with PCOS
A1c ≥ 5.7%, IGT, or IFG on previous testing
Other clinical conditions associated with insulin resistance
History of CVD

Front 116

If a person has no risk factors for diabetes, when should screening begin?

Back 116

In the absence of the above criteria, testing for diabetes should begin at age 45 years.

If results are negative, repeat testing every 3 years, with consideration of more frequent testing depending on initial results and risk status

Front 117

What test results for fasting glucose, glucose tolerance and A1c would indicate pre-diabetes?

Back 117

FPG 100 mg/dl-125 mg/dl: Impaired fasting glucose [IFG]

2-h PG in the 75 gm OGTT 140 mg/dl-199 mg/dl: Impaired
glucose tolerance [IGT]

A1C 5.7-6.4%

Front 118

Four types of auto-antibodies found in type I DM:

Back 118

GADA: glutamic acid decarboxylase autoantibodies
ICA: Islet cell cytoplasmic autoattibodies
IA-2A: Insulinoma associated-2 autoantibodies
IAA: Insulin autoantibodies

Front 119

Pathogenesis of DM Type II

Back 119

Front 120

Manifestations of Beta-Cell Dysfunction in Type 2 Diabetes Mellitus:

Back 120

1. Abnormal pulsatile insulin response (In normal secretion, a spike of insulin is secreted followed shortly by a smaller amount of insulin; this is called “first phase”. In hyperglycemia, the first phase secretion is blunted.)
2. Decreased beta-cell responsiveness to glucose
3. Increased proinsulin to insulin ratio
4. Decreased insulin production:
- Decreased insulin content
- Decreased insulin granule density

Front 121

What is the relationship between atherosclerosis and insulin resistance?

Back 121

Insulin resistance, resulting from genetic and environmental factors, including overnutrition, leads to vasoconstriction, inflammation, and thrombosis.
Inflammation and insulin resistance are reciprocally reinforced, and result in a cycle of accelerated atherosclerosis and increased insulin resistance.

Front 122

What is the only anti-atherogenic adipokine?

Back 122

Adiponectin

Front 123

Adverse effects of ectopic fat:

Back 123

Front 124

Effects of insulin resistance and visceral obesity:

Back 124

Front 125

Relationship between type II diabetes and insulin resistance:

Back 125

Front 126

Glucagon stimulates what enzyme to increase hepatic glycogen breakdown?

Back 126

Glycogen phosphorylase

Front 127

What is the main difference in the cause of ketoacidosis and hyperosmolar hyperglycemic coma?

Back 127

KA is caused by decreased glucose utilization due to insulin deficiency.
HHNS is caused by increased glycogenolysis due to decreased insulin sensitivity.

Front 128

How does a lack of insulin promote the formation of ketone bodies?

Back 128

1. High ratio of glucagon in the portal vein favors the oxidation of fatty acids and formation of ketone bodies.
2. Glucagon blocks glycolysis and decreases availabililty of intermediates required for synthsis of malonyl-coA --> preferential formation of acetyl-coA --> production of ketone bodies

Front 129

Why are endothelial cells effected more by hyperglycemia than other body cells?

Back 129

Because endothelial cells are not able to regulate the amount of glucose they bring in as glucose levels increase, unlike other body cells.

Front 130

According to Dr. Crockett, what are the 2 mechanisms for developing insulin resistance in obesity?

Back 130

1. Adipose cells release FFA's and leptin --> decrease in post insulin receptor signalling.

2. Adipose cells release TNF-a --> decrease in insulin receptor kinase activity.

Front 131

What is the pathogenesis of dyslipidemia in type II diabetics?

Back 131

HDL breakdown is accelerated leading to high levels of free ApoA protein. ApoA is excreted in the urine faster than it can be absorbed --> net loss.
Pathway now shunts over to mostly LDL production.
LDL's are used to make "Small dense" LDL which is highly atherogenic.

Front 132

Diagram of the pathogenesis of vascular disease in diabetes:

Back 132

Front 133

AMA diabetes diagnosis criteria (yet another one):

Back 133

Front 134

Diabetic ketoacidosis mortality rate?

Back 134

10%

Front 135

What are some environment triggers for DM?

Back 135

Front 136

Progression of autoantibody appearance in DM type I

Back 136

Front 137

Is a single autoantibody sufficient to cause DM?

Back 137

No, development of multiple autoantibodies is necessary for development and progression of disease.

Front 138

What type of hyperpigmentation might you see on a Type II diabetic?

Back 138

Acanthosis nigricans:
is often associated with conditions that increase your insulin level, such as type 2 diabetes or being overweight. If your insulin level is too high, the extra insulin may trigger activity in your skin cells. This may cause the characteristic skin changes.

Front 139

Anion gap calculation:

Back 139

AG = [Na+] - [Cl-+ HCO3-]

Front 140

Corrected serum sodium calculation:

Back 140

Corrected [Na+] =

([Na+] + 1.6 x glucose (mg/dL) – 100) / 100