Week 10 Flashcards
1
Q
What is obstructive lung disease and what are the common symptoms?
A
- increased resistance to airflow due to reduced airway radius
- problem is often with expiration (airway collapse due to the inward force imposed by exhalation) → air gets trapped in the alveoli (air trapping)
- bronchoconstriction, inflammation, excess mucus production, reduced alveolar elastic recoil
2
Q
What common obstructive lung diseases have bronchoconstriction?
A
asthma, COPD
3
Q
What common obstructive lung diseases have inflammation?
A
asthma, chronic bronchitis, COPD
4
Q
What common obstructive lung diseases have excess mucus production
A
asthma, chronic bronchitis
5
Q
What common obstructive lung diseases have reduced alveolar elastic recoil?
A
emphysema
6
Q
What is asthma?
A
- bronchial obstruction due to hypersensitive and/or hyperrresponsive immune response
- allergic (extrinsic) or non-allergic (intrinsic)
7
Q
What is the universal response to asthma?
A
- inflammation & edema of muscosa
- increased secretion of thick mucus within airways
- bronchoconstriction
8
Q
What are the symptoms of asthma?
A
- coughing, wheezing, SOB
- coughing up thick mucus
9
Q
What is extrinsic asthma?
A
allergic
- more commonly manifests in childhood (often outgrow it)
- hypersensitivity reaction triggers an immune response
- triggered by inhaled allergens such as dust mite allergens, pet dander, pollen, mold
10
Q
What is intrinsic asthma?
A
non-allergic
- more commonly manifests in adulthood
- hyperresponsive reaction to certain stimuli
- triggered by factors such as anxiety, stress, exercise, cold air, dry air, hyperventilation, viruses, smoke, other irritants
11
Q
Do more people have extrinsic or intrinsic asthma?
A
most people have a combination of allergic and non-allergic asthma
12
Q
What is the pathophysiology of the first stage of an allergic asthma attack?
A
immediate
- sensitized mast cells within the respirators mucosa recognize antigen → release chemical mediators (e.g. histamine) → inflammation, bronchoconstriction, edema, increased mucus secretions →
- also stimulates vagus nerve → bronchoconstriction
13
Q
What is the pathophysiology of the second stage of an allergic asthma attack?
A
- within a few hours
- increased leukocyte infiltration → increased release of chemical mediators → prolonged inflammation, epithelial damage, bronchoconstriction
14
Q
What is a partial obstruction in asthma?
A
- some air is passed through area of obstruction
- less ability to move air out results in air trapping. Attempts to forcefully expire can lead to collapse of the smaller airways
→ residual volume increases → less fresh air inspired, harder to cough out mucus
→ air trapping & hyperinflation over time can stretch out alveoli and cause loss of elasticity
15
Q
What is total obstruction in asthma?
A
- mucus plug completely blocks airflow through narrowed airway
- atelectasis (collapse) of the whole distal to the black
16
Q
What is the goal of treatment for asthma?
A
to minimize the number and severity of acute attacks
17
Q
What are the treatments for asthma?
A
- determine triggers and avoid them if possible
- good ventilation is key
- inhaler if needed or prophylactically (e.g. salbutamol → a Beta-2 adrenergic agonist → bronchodilation)
- other meds: anti-inflammatories (corticosteroids), long-acting bronchodilators
18
Q
What is chronic obstructive pulmonary disease?
A
- a group of chronic respiratory disorders that cause progressive tissue degeneration and airway obstruction
- irreversible and progressive damage to lungs
- 80-90% of cases caused by smoking
19
Q
Which disease is called the disappearing lung disease?
A
emphysema
20
Q
What is emphysema?
A
destruction of alveolar walls
21
Q
COPD is often a combination of which two obstructive lung diseases?
A
emphysema and chronic bronchitis
22
Q
In the pathogenesis of emphysema, smoking or air pollutant + genetic predisposition can lead to…
A
- oxidative stress, increased apoptosis and senescence
- inflammatory cells, release of inflammatory mediators
- protease-antiprotease imbalance (elastase: promotes breakdown of elastic fibers; alpha 1-antitrypsin: anti-protease that inhibits elastase)
… leads to alveolar wall destruction
23
Q
What disease pathogenesis is this sentence describe: cigarette smoke increases oxidative stress & inflammation in alveoli, increases the activity of elastase and decreases effect of alpha1-antitrypsin
A
emphysema
24
Q
What are the two main lung tissue changes in emphysema?
A
- breakdown of alveolar walls
- increased mucus production
25
What is the breakdown of alveolar walls that happens with emphysema?
- decreased SA for gas exchange
- loss of elastic fibers → decreased elastance/increased compliance
- decreased radial traction → collapse of small airways
26
What is the increased mucus production that occurs with emphysema?
- due to chronic inflammation and infection
- leads to thickening and fibrosis of the bronchial walls
27
What are the functional consequences of lung tissue changes in emphysema?
progressive difficulty with expiration
- air trapping and increased residual volume
- overinflation of lungs
- ribs remain in inspiratory position and increased anterior-posterior diameter of chest (barrel chest)
28
What are the consequences of advanced emphysema?
- frequent and more severe infections because secretions are more difficult to remove
- pulmonary hypertension and cor pulmonale in later stages
→ lower ventilation areas causes vasoconstriction to try and match ventilation & perfusion → increased MAP in pulmonary circulation → increased workload of RV → right side CHF
29
What are the symptoms of emphysema?
- dyspnea
- hyperventilation with a prolonged expiratory phase
- fatigue from hypoxia
30
What is the diagnosis of emphysema?
- based on chest x-rays and pulmonary function tests
- increased residual volume and TLC, decrease vital capacity, and inspiratory % expiratory reserve volume
- FEV1and FVC reduced
31
What is the treatment for emphysema?
- avoid irritants and infection
- pulmonary rehab and breathing techniques
- bronchodilators
- high-flow nasal O2 therapy
32
What is chronic bronchitis?
- chronic irritation of the bronchi due to exposure to inhaled irritants (cigarette smoke, industrial or environmental pollution)
- result in chronically inflamed airways with increased mucus production
33
What is the pathogenesis of chronic bronchitis?
inflammation within the bronchial wall → chronic inflammatory response & hyperplasia of mucous glands and other cells in the wall → narrowing of airways & hypersecretion of mucus → airway obstruction and build up of secretions → (lower ventilation → hypercapnia → respiratory acidosis) & alveolar hyperinflation → atrial vasoconstriction in the lungs → pulmonary hypertension and right-sided congestive heart failure
34
What are the symptoms of chronic bronchitis?
- chronic 'productive' cough (secretions are thick and purulent)
- dyspnea
35
What is the diagnosis of chronic bronchitis?
- symptoms
- chest X-rays
36
What is the treatment of chronic bronchitis?
- avoid irritants and infection
- medication & chest therapy to help with expelling mucus
- bronchodilators
- high-flow nasal O2 therapy
37
What are the two types of restrictive lung diseases?
- extra-pulmonary issue limits lung expansion
- lung disease that impairs compliance
38
What causes restrictive lung diseases in which extra-pulmonary issue limits in lung expansion?
- spinal disorders: kyphosis, scoliosis (change in the shape of the spine leads to less efficient breathing)
- disorders of muscle weakness: ALS, muscular dystrophy
39
What causes restrictive lung diseases that impair compliance?
chronic inflammation/irritation → fibrosis → decreased lung compliance
40
What is pulmonary fibrosis?
- a result of long term exposure to irritants
- inflammation → fibrotic tissue → decreased barrier permeability at alveoli
→ decreased compliance (more effort for inspiration, dyspnea, cough)
treatment: ID irritant and remove exposure, treat infection
41
What are the two main vascular issues that affect gas exchange?
pulmonary edema and pulmonary embolus
42
What is pulmonary edema?
- fluid collects around and in alveoli
43
What causes pulmonary edema?
- inflammation within the lungs → increased capillary permeability
- low blood plasma protein level → decreased osmotic P in bloof
- pulmonary hypertension → increased hydrostatic P in blood
44
What are the signs and symptoms of pulmonary edema?
- cough, dyspnea, rales (rattling/cracking noises)
- increased effort to inspired as decrease compliance
- hypoxia
45
What is a pulmonary embolus?
- blood clot that blocks the flow of blood through the lung tissue
- most originate within deep leg veins
46
What are the risk factors of pulmonary embolus?
- immobility
- trauma, surgery
- deep vein thrombosis
- anything that increases risk of blood clots
47
What are the symptoms of pulmonary embolus?
- chest pain, cough
- dyspnea
- SNS response: tachycardia
48
What is the definition of diabetes mellitus?
a chronic disorder of metabolism characterized by elevated plasma glucose levels (hyperglycemia) resulting from defects in insulin production, action or both
49
Where is insulin released from?
released from beta cells of the endocrine pancreas in response to glucose
50
What are the main actions of insulin?
- stimulates glucose uptake into cells (skeletal muscle and adipose) & glucose metabolism
- stimulates anabolic/fed-state metabolism
- inhibits catabolic/fasted-state metabolism
51
How does insulin stimulate anabolic/fed-state metabolism?
- glycogen synthesis
- fatty acid uptake and lipogenesis
- protein synthesis
52
How does insulin inhibit
catabolic/fasted state metabolism?
- fat and glycogen breakdown
- gluconeogenesis
53
What are the mechanisms of insulin-induced glucose uptake?
insulin is required for translocation of the GLUT-4 glucose transporter to the cell surface
→ glucose enters through this transporter into muscle cells and adipose tissue
54
Which two organs do not require insulin for glucose uptake?
liver and brain; but insulin is still important for anabolic processes in these tissues
55
What are the consequences of insulin deficit (impaired production and/or action)?
- decreased glucose uptake into many cells for metabolic and anabolic processes
- impaired lipid, protein & carbohydrate metabolism
56
Prediabetes is a precursor to Type __ Diabetes. What is prediabetes?
II ; blood glucose levels are higher than normal but not yet high enough for type II diabetes diagnosis
57
What is gestational diabetes? How many pregnancies does it effect?
Type II diabetes that develops during pregnancy but disappears after delivery
- ~3-20% of pregnant individuals
- ~5-10% with gestational diabetes will develop type II diabetes later in life
58
What are the signs and symptoms of diabetes mellitus?
- polyuria (frequent urination)
- polydipsia (thirst)
- polyphagia (hunger)
- weight loss (T1DM)
- fatigue
- ketoacidosis (serious) - very rare in T2DM
59
What are the symptoms like in TD1M?
onset is usually acute and intenseW
60
What are the symptoms like in T2DM?
symptoms are usually subtle and insidious
→ often no symptoms for years of decades prior to diagnosis
61
What is osmotic diuresis?
increased urine production due to excess solute filtered into the kidneys
62
What is diabetic ketoacidosis?
- ketone bodies are produced as a byproduct of fatty acid metabolism in the liver
- fatty acids are brought into the mitochondria in the liver and then broken down into ketone bodies → sent out to be used as an alternate source of ATP production in cells around the body
- excess can be excreted in urine → but both of these pathways are rate-limiting meaning if there is too many ketone bodies present in blood at one time → metabolic acidosis
63
What are the signs and symptoms of diabetic ketoacidosis?
fruity breath (acetone), dehydration, nausea/vomiting, hyperventilation, lethargy, confusion, coma
64
Diabetic ketoacidosis happens because...
- the liver produces more glucose to feed body, but without insulin the glucose accumulates in the bloodstream
- body needs to find alternative source of energy and starts breaking down fat producing ketones
65
What are the complications of chronic hyperglycemia?
- macrovascular disease: atherosclerosis
- microvascular disease: retinopathy & nephropathy (microvascular damage due to high blood glucose)
- peripheral neuropathy: nerve degeneration due to ischemia and altered metabolism
66
What is type 1 diabetes?
characterized by autoimmune destruction of β-cells of the pancreatic islets leading to lack of insulin
67
What are the possible predisposing factors of type I diabetes?
genetics, environmental (virus or toxin exposure in early life)
68
What is the treatment for type I diabetes?
- need to replace insulin (injections, pump, islet cell transplant)
- need to tightly monitor blood glucose levels through carful monitoring of food intake and activity levels in relation to insulin administration
69
What type of transplant can be used as a treatment for type 1 diabetes?
islet cell transplants
70
What is type II diabetes?
- characterized by insulin deficit (due to impaired action & production)
- insulin resistance & beta cell destruction
- symptoms are usually subtle (if present at all) and often manifest later in disease progression
71
What are the risk factors for Type II diabetes?
- genetics
- chronic energy imbalance (overnutrition, physical inactivity)
- obesity (chronic inflammation and high FFAs circulating in the blood)
72
What test is used for Type 2 diagnosis?
glucose tolerance testq
73
What is the criteria for diagnosis of T2DM?
- fasting blood glucose ≥ 7.0 mM (126 mg/dL) (prediabetes: 6.1-6.9)
- oral glucose tolerance test ≥ 11.1 mM (200 mg/dL) for 2 hours post-glucose ingestion (prediabetes: 7.8 - 11mM)
74
What is the hemoglobin A1c level test? What is the diagnosis requirement for diabetes and prediabetes?
- glycated hemoglobin
- gives average blood glucose over past 3 months
- ≥ 6.5% for diabetes
- 5.7-6.4% for prediabetes
- gives average blood glucose over past 3 months
75
What is insulin resistance?
insulin is released but its action is impaired
76
What is the etiology and pathogenesis of T2DM?
genetic predispostion + chronic energy imbalance → insulin resistance → increased stress on β cells
initially → β cell compensation: increased insulin secretion (near normal blood glucose levels)
over time → β cell dysfunction ; result: decreased insulin secretion → hyperglycemia
77
what are incretin hormones?
released in the GI tract in the presence of carbohydrates
- bind to receptors on beta cells to increase amount of insulin released by glucose stimulus
78
What makes skeletal muscle cells 'insulin resistant'?
- impaired intracellular signaling in response to insulin binding to its receptor
→ problem with the insulin receptor function or something further downstream the signaling pathway that normally leads to GLUT-4 translocation to the cell surface
- result: less GLUT-4 translocation to the cell surface
79
What are the 3 primary sites of insulin resistance
- skeletal muscles
- liver
- adipose tissues
80
What are the consequences of insulin resistance in skeletal muscles?
- impaired glucose uptake
- impaired anabolic mechanisms (glycogenesis, protein synthesis)
81
What are the consequences of insulin resistance in the liver?
- overproduction of glucose by liver (gluconeogenesis)
- overproduction of fatty acids from glucose (lipogenesis)
82
What are the consequences of insulin resistance in the adipose tissues?
- increased lipolysis → increased free fatty acids circulating in the blood; contributes to further insulin resistance in cells & atherosclerosis risk
83
Along with the consequences of insulin resistance in the liver, adipose tissues, and skeletal muscles, what other cells get damaged from chronic hyperglycemia?
vascular endothelial cells
84
What are the treatment options for T2DM?
- self-managment, education, behaviour change techniques → nutrition & physical activity
- insulin injections (later in disease progression)
- oral hypoglycemic drugs (biguanides, sulfonylureas, thiazolidinediones)
- incretin based therapies (drugs that mimic or enhance the effect or incretin hormones to help increase insulin secretion)
85
What do biaguanides do in terms of treating T2DM? Sulfonylureas? Thiazolidinediones?
Biguanides (e.g. metformin) – suppress liver glucose output and decreased insulin resistance at
skeletal muscles
Sulfonylureas – stimulate insulin production in pancreatic β cells
Thiazolidinediones – decrease insulin resistance at target tissues
86
What type of hormone is GLP1?
incretin hormone
87
What is the main target of GLP1?
beta cells of the pancreas → GLP1 binds to receptors that increases the amount of insulin released (glucose must be present for GLP1 to exert action)
88
Other than increasing the amount of insulin released, what are the other effects of GLP1?
- delays gastric emptying
- decreased food intake
- slows rate of gluconeogenesis
- protects beta cells from apoptosis and stimulates their proliferation
