Final Flashcards
Asthma
- Chronic inflammatory disease of the airways leading to an increase in airway hyperresponsiveness and subsequent recurrent episodes of wheezing, breathlessness, chest tightness and coughing
- Episodes usually associated with airflow obstruction that is reversible
- Incidence: 15-20%
- Mortality reduced by 50% in Canada
Asthma - Triggers
- Non-compliance
- Respiratory tract infections
- Irritants
- Allergens
- GERD
- Anxiety
- Drugs (NSAIDs, beta-blockers)
- Preservatives
- Cold air/exercise
Profile of High Risk Asthmatics
- History of loss of consciousness during attack, intubation, ICU, and frequent ER visits
- Use of beta-agonists in excess
- Night time symptoms
- Limited daytime activities due to asthma
- Poor or very limited respiratory reserve (FEV1<60%)
Canadian Criteria for Asthma Control
Parameters –> Acceptable Control –> Poor Control
- Daytime Symptoms –> less than 3 a week –> 4 or more than a week
- Nighttime Symptoms –> less than 1 a week –> 1 or more a week
- Physical Activity –> normal –> restricted for 3 mos
- Exacerbations –> mild, infrequent –> any in the past year
- Absenteeism –> none –> missed things in the last 3 mos
- PRN rescue inhaler use –> less than 4 a week –> 4 or more a week
Goals of Asthma Control
Reduce Future Risk
- Exacerbations
- Need for acute care
- Need for oral steroids
- Permanent loss of lung function
- Mortality
Reduce/Control Symptoms
- Nighttime symptoms
- Daytime symptoms
- Need for rescue meds
- Improve lung function
- Restore ability to perform daily activities
- Return to normal quality of life
Pharmacologic Asthma Therapy
Control
- Inflammation –> anti-inflammation –> ICS, LTRA, etc.
- Bronchoconstriction –> daily symptom prevention –> LABA, theophylline
Relief
-Bronchoconstriction –> acute symptom relief –> PRN SABA, fast LABA, ICS/LABA
Management Continuum
- Low dose ICS
- Add LABA
- Add LTRA if they do not want ICS
- Prednisone if severe
ICS Side Effects
Common - Reasons for Poor Compliance -Hoarseness -Thrush -Temporary growth delay in kids -Fluid retention Common - Indications of Long Term Problems -Bruising -Fragile skin Common - Clinically Insignificant -Reduced bone density -Suppression of adrenals (>1000 mcg for long periods of time) Uncommon - Serious -Glaucoma -Cataracts
Asthma Treatment
Ciclesonide
-Pro drug that has to land on airway mucosa to activate via esterase
LTRA
-Good or exercise induced or allergies
Blood Glucose Levels
- Normal 3.5-8 mmol/L
- CNS dysfunction occurs at confusion, coma, seizure, death
Maintenance of Glucose Levels
-Post-absorptive state
-Fasting state
-Prolonged starvation
-Substrate availability
+Carbs in food
+Glycogen, glycerol, lactate and amino acids
Insulin
- Master signaling hormone that regulates absorption and usage of fuels
- Produced in the islets of Langerhans in the pancreas
- Secreted in response to glucose
- Actions on Target Cells (adipose, liver, muscle)
1. Induce GLUT4 migration to cell surface in order to transport glucose into the cell
2. Promotes anabolism
Insulin in Fed vs. Non-Fed State
FED (Increased insulin)
- Use glucose everywhere as fuel to generate ATP (enhance uptake)
- Suppress liver production and release of glucose and fat cell lipolysis and release of fatty aids
- Promote synthesis and storage of glycogen, triglycerides, and proteins
NON FED (Decreased insulin)
- Liver makes and releases glucose to feed brain (glycogenolysis, gluconeogenesis)
- Free fatty acids used elsewhere for feul
- Prolonged fast causes ketoacids to be made
Diabetes Mellitus
- Defined as absolute or relative deficiency of circulating insulin leading to impaired use of glucose
- Hyperglycemia occurs due to excess conversion of metabolites to glucose and less utilization of glucose in the body
- Leads to disordered carb, fat and protein metabolism
- Leading cause of blindness, end stage renal disease, lower limb amputation, and CV disease
Diabetes Mellitus - Diagnosis
ONE of the following at least twice
- Fasting blood glucose > 7 mmol/L (N < 6)
- Casual blood glucose > 11.1 mmol/L + symptoms of polyuria, polydipsia, and weight loss
- 2h blood glucose in a 75 g OGTT > 11.1 mmol/L (N < 7.8)
Diabetes Mellitus: Type 1
-Insulin dependent
-Autoimmune destruction of pancreatic beta cells
-Once symptoms arise, there is already 60-80% destruction
-Insulitis: mononuclear and cytotoxic T cells clustering around and within individual islets (inflammation)
-Prone to diabetic ketoacidosis
+Insulin drops causing adipocytes to breaks on mobilization of fatty acids to fail –> fatty acids pour out and go to liver where they are converted into ketoacids
Diabetes Mellitus: Type 1 - Pathogenesis
Three interlocking mechanisms responsible for islet cell destruction
- Genetic susceptibility - 90% risk linked to MHC polymorphism
- Autoimmunity
- Chronic, multistage process required to overcome self tolerance
- Specific destruction of beta cells
- T cell mediated injury - Environmental trigger
Diabetes Mellitus: Type 1 - Treatment
-Exogenous insulin administered several times/day with monitoring
-Emerging Therapies
+Cadaveric islet transplants
+Cultured islet (stem cells)
+Immunemodulation
+Vaccine
Diabetes Mellitus: Type 2
- Non-insulin dependent
- Prevalence increases with age and half are undiagnosed
Diabetes Mellitus: Type 2 - Major Metabolic Defects
-Peripheral insulin resistance in muscle and fat
-Decreased pancreatic insulin secretion
-Increased hepatic glucose output
+Liver less able to sense insulin and thinks the body is fasting so it pours out glucose
Diabetes Mellitus: Type 2 - Insulin Resistance
-Present 10-20 years before onset
-Best predictor of future diabetes
-Means too much fasting response and too little fed response
+Decreased glucose uptake after eating, protein synthesis, and triglyceride uptake by fat cells
+Increased hepatic production and release of glucose, lipolysis, and circulating FFAs
+Maldistribution of fat - there is an inverse relationship between fasting plasma fatty acids and insulin sensitivity (especially viscera fat)
Diabetes Mellitus: Type 2 - Natural History
-Islet cells try to help and start secreting more insulin, but it is contending with resistance and eventually cells poop out –> hyperglycemia
Diabetes Mellitus: Type 2 - Treatment
LIVER - Glucose Production by making liver more sensitive to insulin
- Biguanides (Metformin)
- Thiazolidinediones
INTESTINE - Glucose Absorption by blocking breakdown of carbs in gut so glucose not made as quickly and therefore not absorbed as fast
-Alpha-glucosidase inhibitors
PANCREAS - Insulin Secretion
- Sulfonylureas and meglitinides (augment insulin secretion)
- Dipeptidyl peptidase 4 inhibitors
- GLP-1 analogue (interacts with different receptors on beta islet cells to modulate insulin output)
- Insulin
ADIPOSE/MUSCLE - Peripheral glucose uptake, altered fat cells, less insulin resistance –> try to change bad adipocytes to more benign, subcutaneous fat cells
-Thiazolidinediones
Diabetes Mellitus - Acute Complications
- Hyperglycemia Symptoms
- Threshold for kidney to resorb glucose is 10 mmol/L and anything more appears in urine –> osmotic diuresis
- Polyuria and polydipsia - Diabetic Ketoacidosis (T1DM)
- Triggered by absolute absence of insulin
- Hyperglycemia –> dehydration –> loss of sodium, potassium, etc. –> very elevated levels of ketoacids –> metabolic acidosis - Hyper-osmolar Non-Ketotic Coma (T2DM)
- >50 years, especially debilitated on diuretics - Hypoglycemia
- Due to too much insulin or hypoglycemic agent
- Diagnosed as glucose levels <2.5 mmol in men and 2.0 in women
- Symptoms: Activation of SyNS to secrete catecholamines leading to anxiety, palpitations, sweating, hunger, pallor, etc.; CNS dysfunction
- Reversal of symptoms by correction of glucose concentration
Treatment of Diabetic Ketoacidosis and Non-Ketotic Coma
-Treat underlying cause
-Fluid resuscitation
-Insulin infusion
+DKA: Stops ketoacidosis
+Non-Ketotic Coma: Lowers glucose but patients are very sensitive –> dose and monitor
Diabetes Mellitus - Chronic Complications
- Accelerated Atherosclerosis
- Coronary artery disease (MI/angina)
- Cerebral vascular disease (stroke)
- Peripheral vascular disease (claudication, gangrene) - Diabetic Nephropathy
- Characteristic deposit in glomeruli
- Initial hyperfunctioning followed by gradual decline
- Increase in protein loss in urine - Diabetic Retinopathy
- Diabetic Neuropathy
- Diabetic Foot
- Vascular disease leads to poor circulation
- Loss of limb due to gangrene arising from infection
Diabetes Mellitus - Monitoring
Glycemic Control -Venous blood glucose -Capillary glucose monitoring \+Small portable meters; finger prick -Glycated hemoglobin (HbA1C) \+Product of non-enzymatic and irreversible binding of glucose to circulating hemoglobin \+Increase average glucose concentration and proportion of HbA1C \+3 month overview of glucose control
Kidney (urinary protein excretion)
-24 h urine protein excretion
-Microalbuminuria
+Proteinuria begins with small amounts (<300 mg/dL)
Diabetes Mellitus - Treatment
-Glycemic control
-Foot care
-Modification of other risk factors or coronary artery disease
-Prevention of neuropathy
-Prevention of retinopathy - laser to prevent retinal detachment
-Prevention of nephropathy
+Tight control of BP
+Tight control of glucose
+Angiotensin converting enzyme inhibitor or ARB in presence of microalbuminuria
Ocular Anatomy - Sclera
GLOBE - ANTERIOR SEGMENT
- Outer coat of the eye
- White appearing collagenous structure (0.1-0.3 mm thick)
- Site of insertion of extraoccular muscles
- Posterior perforation allows for entry of optic nerve
- Blocks extraneous light from entering globe
PATHOLOGY
- Scleritis (autoimmune and infections)
- Scleral lacerations
- Can be ruptured by direct trauma
Ocular Anatomy - Conjunctiva
GLOBE - ANTERIOR SEGMENT
- Modified mucous membrane that covers the inside surface of the lids (tarsals) and the globe to the edge of the cornea (bulbar)
- Protects the globe
PATHOLOGY
-Infections
+Viral conjunctivitis (pink eye)
+Bacterial conjunctivitis
-Allergic conjunctivitis
-Steven-Johnson Syndrome
+Hypersensitivity reaction of skin and mucous membranes, often secondary to medications
+Inflammation of conjunctiva results in adhesions between bulbar and tarsal conjunctiva
+Complications
(a) Limbal stem cell deficiency with resultant corneal scarring
(b) Severe dry eye (keratoconjunctivitis sicca)
Ocular Anatomy - Cornea
GLOBE - ANTERIOR SEGMENT
- Optically clear “watch-glass” over visual axis
- Continuous with sclera
- 5 Specialized Layers
1. Epithelium - stratified squamous
2. Bowman’s Membrane - specialized collagen
3. Stroma - regular array of collagen and mucopolysaccarides
4. Descemet’s Membrane - basement membrane
5. Endothelium - metabolically active monolayer (controls hydration)
PATHOLOGY
-Acute
+Corneal abrasion - traumatic loss of epithelium
+Corneal ulcer - microbial infection of cornea characterized by a white infiltrate +/- hypopyon (WBC)
-Chronic
+Viral infections - herpes simplex keratitis produces dendritic staining pattern and may lead to loss of corneal sensation
+Trauma - can lead to iris coming off and migrating to plug hole
Ocular Anatomy - Iris
GLOBE - ANTERIOR SEGMENT
- Anterior extension of ciliary body/uveal tract
- Forms the pupil
- Contains sphincter muscle to constrict pupil and dilator muscle to dilate pupil
- Pupil size varies with light intensity
PATHOLOGY -Iritis (Anterior Uveitis) \+Inflammation of uveal tract \+Often idiopathic, but maybe related to systemic autoimmune/inflammatory conditions \+Symptoms: Photophobia, pain, redness \+Treatment: Topic steroid eye drops
Ocular Anatomy - Ciliary Body
GLOBE - ANTERIOR SEGMENT
- Located behind iris, part of uveal tract
- 6-7 mm wide
- 3 Main functions
1. Ciliary muscle produces accommodation for near vision via action on lens (through zonules)
2. Vascular supply involved in production of aqueous humour, which provides metabolic support for the lens and cornea
3. Facilitates drainage of aqueous through actions on trabecular network
PATHOLOGY: Glaucoma
- Progressive optic neuropathy characterized by typical optic nerve head and visual field changes
- Treatment: Involves lowering IOP by decreasing aqueous production by ciliary body or increasing aqueous outflow via trabecular meshwork and ureoscleral outflow paths
Ocular Anatomy - Lens
GLOBE - ANTERIOR SEGMENT
- Focuses light onto retina
- Optically clear structure that grows throughout life contained within basement membrane
- Attached to ciliary body by 60-80 zonules
- Accommodates to allow near vision as controlled by ciliary muscle
PATHOLOGY: Cataracts
-Opacity of the lens that may be
+Posterior subcapsular (trauma, steroids, diabetes)
+Nuclear sclerosis (age)
+Cortical (age, trauma)
-Treatment: Surgically remove and replace lens with intraocular lens implant to help focus light on retina
Ocular Anatomy - Choroid
GLOBE - POSTERIOR SEGMENT
- Posterior extension or urea between sclera and retina
- Supplies oxygen to retinal pigment epithelium and outer 1/3 of retina
- Most vascular layer with highest rate of blood flow per gram in body
- Carries 70% of blood flow in eye
PATHOLOGY
- Malignant melanoma
- Age-related macular degeneration (AMD)
Ocular Anatomy - Retina
GLOBE - POSTERIOR SEGMENT
- 10 layer structure that transforms light to an electrochemical signal (phototransduction)
- 0.1-0.2 cm thick
- Light penetrates outer 8 layers to reach rods and cones
- Retinal pigment epithelium supports metabolic activities of rods and cones
Ocular Anatomy - Macula
GLOBE - POSTERIOR SEGMENT
- Centre of retina that produces detailed vision
- Centre of macula is fovea
- Location of cones
Ocular Anatomy - Retinal Pigment Epithelium
- Monolayer of cells between retina and choroid
- Provides special metabolic and ionic conditions necessary for rods and cones, and is essential for normal vision
- Aging changes RPE-choroid interface and may result in changes of AMD
PATHOLOGY: Age-Related Macular Degeneration
-Dry (Atrophic) Form
+Non-neovascular
+Characterized by drusen and RPE atrophy
+Usually results in modest visual changes only
-Wet (Exudative) Form
+Neovascular
+Characterized by pathological choroidal neovascularlization
+Fibrosis and subsequent damage to overlying retina results in significant central visual loss
Ocular Anatomy - Vitreous
GLOBE - POSTERIOR SEGMENT
-Semi-solid mixture of water, collagen and hyaluronic acid
-Optically clear, fills centre of globe
-Functions
+Maintains optically clear media
+Thermoregulation
+Shock absorption
+Maintenance of relative hypoxia
-Age-related reduction in hyaluronate results in opacities (floaters)
-Firm adhesions to optic nerve, macula, retinal blood vessels, and peripheral retina at ora serrata can produce retinal tears with age-related condensation and liquefaction
Ocular Anatomy - Optic Nerve
GLOBE - POSTERIOR SEGMENT -Axons of retinal ganglion cells converge to form optic nerve -Ends at optic chiasm and its axons synapse at lateral geniculate body -Pathology may be due to \+Glaucoma \+Optic neuritis/inflammation \+Ischemia \+Compression \+Toxic
Ocular Anatomy - Eyelids
ADNEXAL STRUCTURES
- Protects corneal surface
- Lid contains muscle, the tarsal plate, and is the site of attachment of the orbital septum
- Lid opening is via levator palpebrae (CN III) and Muller’s muscle (SyNS)
- Lid closing is via orbicularis oculi (CN VII)
Ocular Anatomy - Bony Orbital Walls
ADNEXAL STRUCTURES
- Provides protection for the globe
- Pyramid in shape with apex at back
- 7 bones
- Volume 30 mL
- Nerves and blood vessel supply globe pass through foramina in bones
