SEARCH RESULTS FOR: pneumonia

Hyperosmolar Hyperglycemic State

Hyperosmolar Hyperglycemic State (HHS) Note: HHS is only seen in Type II DM patients! Note: In patients with either DKA or HHS, always look for an underlying cause (i.e. an infection) Author: Yan Yu Reviewers: Peter Vetere Gill Goobie Hanan Bassyouni* * MD at time of publication Alters total body water & ion osmosis Inadequate insulin production, insulin resistance, non- adherence to insulin Tx Relative Insulin deficit Stresses that ↑ Insulin demand: infections, pneumonia, MI, pancreatitis, etc) Hyperglycemia (Very high blood [glucose], higher than in DKA) When blood [glucose] > 12mmol/L, glucose filtration > reabsorption, ↑ urine [glucose] Glucosuria Glucose in filtrate promotes osmotic diuresis: large- volume urine output Polyuria Dehydration (↓ JVP, orthostasis: postural hypotension/ postural tachycardia, ↑ resting HR) Some insulin still present, but not enoughsome glucose is utilized by muscle/fat cells, some remain in the blood Cells not “starved”, but still need more energy ↑ release of Catabolic hormones: Glucagon, Epinephrine, Cortisol, GH Body tries to ↑ blood [glucose], to hopefully ↑ cell glucose absorption Hypothalamic cells sense low intra-cellular glucose, triggering feelings of hunger Polyphagia Note: the presence of some insulin directly inhibits lipolysis; thus, in HHS there is no ketone body production, and no subsequent metabolic acidosis and ketouria (unlike in DKA). If ketones are detected in an HHS patient it’s likely secondary to starvation or other mechanisms. ↓ ECF volume, ↑ ECF osmolarity (i.e. hypernatremia) ↑ Gluconeogenesis ↑ Glycogenolysis (in liver) ↓ Protein synthesis, ↑ proteolysis (in muscle) ↑ Gluconeogenic substrates for liver If the patient doesn’t drink enough water to replenish lost blood volume If pt is alert and Electrolyte imbalance water is accessible Water osmotically leaves neurons, shrinking them Neural damage: delirium, lethargy, seizure, stupor, coma ↓ renal perfusion, ↓ GFR Renal Failure (pre-renal cause; see relevant slides) Polydipsia Note: in HHS, body K+ is lost via osmotic diuresis. But diffusion of K+ out of cells may cause serum [K+] to be falsely normal/elevated. To prevent hypokalemia, give IV KCl along with IV insulin as soon as serum K+ <5.0mmol/L. But ensure patient has good renal function/urine output first, to avoid iatrogenic hyperkalemia! Note: Electrolyte imbalances (i.e. hyperkalemia, hypernatremia) are worsened by the acute renal failure commonly coexisting with DKA/HHS Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 3, 2016 on www.thecalgaryguide.com

Lung cancer clinical findings and paraneoplastic syndromes

Lung cancer: clinical findings and paraneoplastic syndromes Note: most presentations of lung cancer are very subtle with non-specific symptoms and signs (i.e. fever, weight loss, general malaise) Obstruction of proximal airway Inability to clear inhaled pathogens Postobstructive pneumonia Cough, fever, dyspnea Local tumor growth Spread of tumor to pleural surface Chest Pleural discomfort effusion • Obstruction or compression at local site Uncontrolled abnormal cell growth in one or both lungs 4 Lung Cancer Airway invasion Hemoptysis Lambert-Eaton syndrome (Production of auto-antibodies against Calcium channels) Muscle weakness I` effort to Compression at the Compression Superior vena ventilate the laryngeal nerve of brachial cava lungs nerve plexus compression Impaired innervation to the vocal cords Dyspnea Shortness of Arm/shoulder/ Face/arm breath Voice hoarseness neck pain edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Authors: Yoyo Chan Reviewers: Midas (Kening) Kang Usama Malik Leila Barss* * MD at time of publication Tumor secretes biologically active substances Paraneoplastic Syndromes 4 Associated symptoms with malignant diseases TGF131 extracellular matrix protein Fingers clubbing PTHrP T calcium release from bones Hypercalcemia Serum calcium >2.6 mmol/L ADH 1 SIADH T water reabsorption 1 Hyponatremia Serum sodium <135mEq/L Abbreviations: • ACTH: Adrenocorticotropic hormone • ADH: Anti-diuretic hormone • PTHrP: Parathyroid hormone-related protein • SIADH: Syndrome of inappropriate antidiuretic hormone production • TGFI31: Transforming growth factor beta 1 1` ACTH cortisol release and production Cushing's syndrome (symptoms and signs caused by prolonged cortisol exposure) Muscle weakness, hyperglycemia, severe hypokalemia

Orbital Cellulitis: Pathogenesis and clinical findings

Orbital Cellulitis: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Jaimie Bird Dr. Rupesh Chawla* * MD at time of publication Staphylococcus aureus, Streptococcus pyogenes Note: Orbital cellulitis is an extremely serious infection. If not caught and treated early, it can lead to death. CT should be performed if suspected. Involves the orbit Panopthalmitisb Endopthalmitisc Blindness Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenza Local infection or break in skin Eye surgery or trauma Direct inoculation Sinusitis (more common) Periorbital cellulitis1,2 Hematogenous spread Contiguous spread of infection Pathogens reach orbital tissue (posterior to the orbital septum) Spreads to periorbital tissue (anterior to the orbital septum) Localized inflammation Conjunctival chemosisa Eyelid and periorbital edema Pain on palpation Induration Warmth Orbital Cellulitis Inflammation of orbital tissue Proptosis Spreads to surrounding structures Subperiosteal abscess Brain abscess Cavernous sinus thrombosis Meningitis Subdural empyema Orbital abscess Notes: Impinges on ocular muscles Impaired extra- ocular movements Pain with eye movement or opthalmoplegia Definitions: Impinges on nerves Afferent pupillary defect Decreased visual acuity Exposes cornea Corneal drying and scarring a. Chemosis: Edema of the bulbar conjunctiva b. Panopthalmitis: inflammation of all coats of the eye including intraocular structures. c. Endopthalmitis: inflammation of the interior of the eye. 1. See slide on Periorbital Cellulitis for how sinusitis can lead to the development of periorbital cellulitis 2. The micro-organism responsible for periorbital cellulitis varies depending on how the pathogen was introduced to the system. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Periorbital Cellulitis: Pathogenesis and Clinical Findings

Periorbital Cellulitis: Pathogenesis and Clinical Findings Authors: Amanda Marchak Reviewers: Jaimie Bird Dr. Rupesh Chawla* * MD at time of publication Staphylococcus aureus, Streptococcus pyogenes (most common organisms) Note: Also referred to as preseptal cellulitis Dacryoadenitisa Conjunctivitisb Acute chalazionc Dacryocystitisd Hordeolume Streptococcus pneumoniae, Moraxella catarrhalis, non-typable Haemophilus influenza (most common organisms) Abrasion Insect bite Burns Trauma Local infection Contiguous spread of infection Sinusitis Otitis media Hematogenous spread Local break in skin Micro-organisms enter Definitions: Note: Eye exam should reveal normal: - extra-ocular movements and globe position - pupillary reflex and visual acuity If any are abnormal, the presentation is no longer considered periorbital cellulitis, as the infection has likely spread beyond the preseptal compartment/orbital septum. If the eye cannot be assessed, the patient NEEDS a CT scan. Pathogens reach dermis and subcutaneous periorbital tissue Periorbital Cellulitis a. Dacryoadenitis: infection of the lacrimal glands b. Conjunctivitis: inflammation of the conjunctiva c. Chalazion: a benign, painless bump or nodule inside the upper or lower eyelid which results from healed internal hordeolums that are no longer infectious. d. Dacryocystitis: an infection of the lacrimal sac, secondary to obstruction of the nasolacrimal duct at the junction of lacrimal sac. e. Hordeolum: localized infection or inflammation of the eyelid margin involving hair follicles of the eyelashes or meibomian glands. Spreads beyond preseptal compartment/orbital septum Involves the orbit Orbital cellulitis See slide on Orbital Cellulitis: Pathogenesis and clinical findings Localized inflammation Pain on palpation Induration Warmth Eyelid and periorbital edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Scarlet Fever: Pathogenesis and clinical findings

Scarlet Fever: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Note: GAS pharyngitis can be left untreated, but scarlet fever MUST be treated. Enters systemic circulation Delayed type hypersensitivity response See slide on Type IV Hypersensitivity: Pathogenesis and Clinical Findings Abbreviations: GAS – Group A Streptococci SPE – Streptococcal Pyogenic Exotoxin SSA – Streptococcal Superantigen Group A Streptococci Infection1 5-15 years old2 Adhesins, including lipoteichoic acid and M protein, within GAS cell wall facilitates regional adherence to pharyngeal epithelial cells GAS releases SPE A, B and C, and SSA Stimulation of T-cells and mononuclear cells General inflammatory response White strawberry tongue3 Coating sluffs off after 2-3 days Red strawberry tongue4 Complications: See slide on Group A Streptococci Pharyngitis: Pathogenesis and Clinical Findings Scarlatiniform rash (sandpaper feel) 0-1 days post- pharyngitis Pastia’s lines5 1-2 days post- pharyngitis Appears on upper trunk and axillae 3-4 days post- pharyngitis Spreads to remainder of body, sparring face6, palms and soles 7-10 days post- pharyngitis Fades Desquamation7 Otitis media, sinusitis, pneumonia, bacteremia, osteomyelitis, meningitis, arthritis, erythema nodosum, hepatitis, acute poststreptococcal glomerulonephritis, and acute rheumatic fever Fine maculopapular rash Blanchable with Non-pruritic and pressure painless Notes: 1. While the majority of infections are cases of GAS pharyngitis, rarely, it is possible to develop scarlet fever from a GAS skin infections. 2. Scarlet fever is most common in patients of this age group although, rarely, it can occur in adults. 3. White strawberry tongue is characterized by a white coating on the tongue through which edematous lingual papillae project. 4. Red strawberry tongue is characterized by a beefy red, edematous tongue covered in edematous lingual papillae. 5. Prominent erythema and petechiae in the body folds, especially the antecubital fossae and axillary folds. They tend to appear before the rash and persist through the desquamation phase. 6. Typically, the rash does not occur on the face, although facial flushing may be noted. When this occurs, there is perioral sparring. 7. Desquamation tends to occur ~1 week after the rash fades, most severely effecting the hands and feet, and lasts 2-6 weeks. While a classical presentation, not everyone gets it. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Sinusitis: Pathogenesis and clinical findings

Sinusitis: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Abbreviations URTI – Upper respiratory tract infection Nasal obstruction/ congestion Hyposmia Headache Facial pain/pressure Maxillary tooth pain Ear pain/ fullness Osteomyelitis of frontal bone Chemical irritants Cystic Fibrosis Direct toxic effect on cilia Viral URTI Allergies Inflammation of paranasal sinuses Edematous passageways Septal deviation Adenoid hypertrophy Polyps Turbinate hypertrophy Tumors Foreign body Dysfunctional cilia Congenital and/or craniofacial abnormality Obstruct sinus ostia Cilia unable to clear mucus from sinuses Mucus unable to drain through ostia Post-nasal drip Mucus overflows from the sinuses Cough Mucus accumulates in sinuses Occupies a larger volume Applies ↑ pressure to sinus walls Mucopurulent discharge Bacterial1 overgrowth in sinuses Bacterial infection spreads to adjacent structures Halitosis Pharyngitis Throat clearing Dental root infection Immunodeficiency Note: Irritates the back of the throat Perforation of the Schneiderian membrane2 Passage of bacteria into the sinuses Fever Fatigue Subperiosteal orbital abscess Orbital abscess Orbital edema ↑ susceptibility to bacteria 1. The most common bacteria are Streptococcus pneumoniae, Haemophilus influenza, and Moraxella catarrhalis. Staphylococcus aureus and Group A Streptococcus may be seen, but are less common. However, in cases of dental root infection, oral anaerobes become more common, while Pseudomonas species are associated with foreign bodies. 2. The Schneiderian membrane is the membranous lining of the maxillary cavity. Cavernous sinus thrombosis Meningitis Cerebral abscess Subdural abscess Epidural abscess Periorbital or orbital cellulitis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Tonsillitis: Pathogenesis and clinical findings

Tonsillitis: Pathogenesis and clinical findings Group A Streptococci (GAS) infection1,2 Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Viral pathogen1 5-15 years3 Pathogen colonizes the nasopharynx Pathogen colonizes oropharynx4 ** ↑ vascular permeability Leakage of protein and fluid into surrounding tissue Inflammatory cytokine release Inadvertent cellular injury and hemolysis Tonsillar petechiae and erythema Systemic inflammatory cytokines disrupt hypothalamic regulation Fever White blood cell (WBC) activation WBCs infiltrate site of infection WBCs kill pathogen Accumulation and deposition of cellular debris and products of inflammatory response Tonsillar exudate Note: *When GAS is the pathogen, cytokine release and WBC activation is secondary to the release of exotoxins by GAS. Swelling and irritation ↑ lymph drainage to regional nodes Enlarged anterior cervical nodes Cough Note: It is extremely important to distinguish between viral tonsillitis and bacterial tonsillitis. Viral tonsillitis is usually self-limited while GAS tonsillitis can be associated with a number of complications. Notes: Tonsillar tissue Tonsillar edema Nasal tissue6 Nasal congestion Coryza Nasal discharge irritates back of throat Complications5: Peritonsillar abscess, neck abscess, otitis media, sinusitis, pneumonia, scarlet fever, bacteremia, osteomyelitis, meningitis, arthritis, erythema nodosum, hepatitis, acute poststreptococcal glomerulonephritis, acute rheumatic fever, and toxic shock syndrome 1. In general, viral tonsillitis is more common than GAS infection. However, in the absence of cough and coryza (acute, isolated tonsillitis), GAS is more common. 2. While GAS is the most bacterial cause of tonsillitis, it can be caused by other pathogens. 3. GAS tonsillitis is most common in patients of this age group although, rarely, it can occur in adults. 4. When GAS colonizes the oropharynx, the primary location of infection determines how it’s identified. • tonsils primarily effected = tonsillitis • pharynx (throat) primarily effected = pharyngitis (See slide on Group A Streptococci Pharyngitis: Pathogenesis and Clinical Findings) • both = pharyngotonsillitis 5. The listed complications are the result of exotoxins entering systemic circulation or the bacterial infection extending beyond the tonsils. 6. While viral tonsillitis tends to be associated with more upper respiratory tract symptoms, clinical signs and symptoms are NOT reliable for diagnosing GAS tonsillitis. Throat swab or rapid antigen detection test are the standards for diagnosis. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Hypoxemia- Pathogenesis and clinical findings

Hypoxemia- Pathogenesis and clinical findings interstitial lung disease pulmonary hypertension thickening of interstitium vasculature diffusion across alveolar membrane diffusion limitation exertional desaturation PE AVM pneumonia atelectasis cardiac defects airways disease inefficient blood flow ventilated areas blood bypasses aerated alveolar tissue V:Q mismatch R L shunt negligible significant improvement paO2 response 100% O2 Central drugs coma hypothyroidism peripheral damaged lung structure chest wall disorders minute ventilation alveolar gas exchange altitude barometric pressure driving pressure diffusion across membranes inspired a-a gradient hypoxemia tissue hypoxia cyanosis anaerobic metabolism organ brain anoxic angina

Ataxia Telangiectasia Pathogenesis and Clinical Findings

Ataxia-telangiectasia: Pathogenesis and clinical findings Genetics: Autosomal Recessive, with a defect on gene region 22 and 23 on Chromosome 11q Authors: Merna Adly Reviewers: Kara Hawker Crystal Liu Yan Yu* Laurie Parsons* * MD at time of publication Truncation and loss of the ATM protein, a serine/threonine protein Kinase Impaired ability to phosphorylate ATM, a key protein involved in the activation of the DNA damage checkpoint Impaired DNA damage and apoptosis signals Impaired ATM concentration ability at DNA damaged sites Failure to activate apoptosis in specific neural regions Genomically-damaged cells incorporated into the developing nervous system Progressive spinocerebellar granular neural cell damage and Purkinje Cell degeneration Cerebellar Ataxia (at 12-18 months); involuntary muscle contractions, hypotonia, IQ decline, and abnormal eye movement Loss of ATM leads to mitotic defects and arrest in gamete genetic recombination process Gonadal dysgenesis and delayed puberty DNA damage to tumor suppressors such as p53 and BRCA1 Impaired signaling of downstream cell cycle regulators Impaired genome stability and increased disposition to cancer ↑ Acute Lymphocytic Leukemia of T cell origin (in children) and Chronic Lymphoblastic Leukemia (in adults) Impaired recombination of DNA in immune cells Thymic hypoplasia; humoral & cellular immunodeficiency ↓ or absent functional immunoglobulins IgA, IgE, and IgG2 that function to prevent respiratory infections Respiratory infections with bronchiectasis and pneumonia Cells less able to undergo apoptosis in response to ionizing radiation Accumulation of DNA defects in the cells of sun exposed areas such as skin, hair, and conjunctiva Mucocutaneous telangiectasia on the bulbar conjunctiva and ears between 2-6 years of age May progress to involve periorbital skin, trunk, extremities, body folds, and other mucosal surfaces Sterility DNA damage and genomic instability Premature melanocyte stem cell differentiation Premature graying of skin and hair Abbreviations: • ATM – Ataxia-telangiectasia mutated protein • p53 – Tumor protein 53 • BRCA 1 – Breast cancer susceptibility protein. • IgA, IgE, IgG2 – Immunoglobulins Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 4, 2019 on www.thecalgaryguide.com

pertussis-pathogenesis-clinical-findings-and-complications

Pertussis: Pathogenesis, clinical findings and complications Authors: Morgan Sosniuk Yan Yu* Reviewers: Jessica Tjong Crystal Liu Timothy Fu Luis Murguia-Favela* * MD at time of publication Bordetella pertussis bacterium enters the airway via droplets B. pertussis binds to ciliated epithelial cells and multiplies, colonizing the nasopharynx B. pertussis produces multiple toxins (e.g. “pertussis toxin”, “tracheal toxin”) which damage mucosal cells Pertussis toxin produces cyclic AMP (cAMP) and disrupts normal intracellular signalling, impairing the immune response initially Pertussis (“Whooping Cough”) Respiratory syndrome consisting of severe fits of paroxysmal coughing and stridor Nasopharyngeal swab produces positive culture and/or positive PCR result (either is diagnostic) Initial immune dampening allows the bacteria to take hold and begin replicating. During this “incubation period”, the bacteria has not yet replicated to the point of causing symptoms. 1. Catarrhal Stage (5-10 days) After a few days, continued damage to nasopharynx epithelial cells stimulates the immune system to ↑ its response once again 2. Paroxysmal Stage (1-2 weeks) Tracheal cytotoxin released by B. pertussis impairs normal cilia function and ciliary beating in the trachea 3. Convalescent stage (2 weeks - months) Immune defenses successfully eliminate the majority of B. pertussis from the respiratory tract ↑ mucus production from goblet cells of the respiratory epithelium Mucus blocks airway, prevents air entry Collapsed lung Rarely, areas of chest or abdominal wall are weakened, allowing contents to bulge out Hernia ↑ proinflammatory cytokine production Mild fever Cold-like symptoms Mild dry cough, runny nose, sneezing, nasal congestion ↓ fluid clearance from the respiratory tract Fluid in the trachea narrows tracheal diameter “Whooping” cough Severe, rapid and sequential coughing fits, followed by characteristic “whooping” sound on inspiration due to a stridor from a narrower trachea Fluid build up in the lungs Environment more susceptible to co-infection Other bacteria colonize the lungs Pneumonia Paroxysmal coughing fits ↓ in frequency and number Cough may sound louder (mechanism unknown) but overall symptoms ↓ Some B. pertussis still remain Residual cough flares This stage may be prolonged in unvaccinated individuals who eliminate the bacterium more slowly Intense cough can break ribsàsharp rib ends puncture lungàair leaks out ↑ pressure on bladder If weak urethral sphincters: Urinary incontinence Cough ↑ intra- abdominal pressure If dripping mucus triggers gag reflex while a cough is contracting abdominal muscles: Vomiting Coughing fits disrupt regular inspiration and ↓ oxygenation Hypoxia If hypoxia is profound enough to affect brain Seizures Abdominal muscles tire from coughing, and coughing fits make it difficult to sleep Extreme fatigue Rarely, violent coughing causes trauma to head Intracranial hemorrhage Vertebral or carotid dissection Cerebral ischemia Coma or death Notes: • B. pertussis is a Gram- negative strict aerobe • An effective vaccine exists to prevent infection by B. pertussis • Pertussis most commonly infects children <18 months prior to completion of scheduled vaccination series, or adolescents with ↓ immunity Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 4, 2020 on www.thecalgaryguide.com Include a sentence! When sending in the final draft of a slide, please include in the email a sentence that describes the slide that you've produced in detail. This will help us boost the relevance of the slide with search engines. E.g., Disease X presents with symptom Y due to pathophysiology Z Pertussis presents with fits of severe paroxysmal coughing due to impaired mucociliary clearance.

Creutzfeldt-Jakob-Disease

Creutzfeldt-Jakob Disease: Pathogenesis and clinical findings Author: Skye McIntosh Reviewers: Heather Yong Tony Gu Davis Maclean *Scott Jarvis *Gary Klein *Yan Yu * MD at time of publication Familial (5-15%): Autosomal dominant inheritance of pathologic prion protein (PRNP) genes Sporadic (85%) Pathologic prion protein (PrPSc) form spontaneously from normal prion protein isoforms (PrPc) Acquired (<1%) Variant: consuming bovine spongiform encephalopathy (BSE) infected beef (mad cow disease) Iatrogenic: related to medical intervention (e.g instruments contaminated with PrPSc) Note: The normal prion protein isoform (PrPc) is expressed predominantly in neurons. It is not intrinsically pathological. Presence of PrPSc kickstarts an “autocatalytic” process by which existing PrPSc converts more normal prion protein (PrPc) into pathological protein. Pathological prion proteins (PrPSc) enter host Astrogliosis: ↑ astrocyte cells infiltrate and occupy the space of lost neurons Vacuolation or spongiform changes: clusters of small vacuoles in synaptically dense cortical areas Pathologic prion proteins (PrPSc) are insoluble and aggregate within neurons Mechanism unknown Neuronal loss Creutzfeldt-Jakob Disease Fatal infectious brain disorder causing neuronal death Diffuse brain atrophy Exact mechanism unknown Frontal lobe atrophy The frontal lobes are responsible for executive function and personality Occipital lobe atrophy The occipital lobes are responsible for interpreting vision Basal ganglia atrophy The basal ganglia is responsible for sequencing voluntary movements Loss of inhibitory cortical neurons Hyper-excitable cortical neurons Myoclonus: quick involuntary muscle jerks Cerebellar atrophy The cerebellum is responsible for coordination and fine correction of movements Gait Slurred Extensive neuronal loss in the brainstem reticular activating system Coma Impaired control of respiratory muscles Pneumonia and respiratory failure ~ 75% mortality within 1 year Rapidly progressive dementia Anxiety, depression Visual hallucinations Double vision Bradykinesia: Tremor Rigidity: ↑ muscle tone ataxia speech Incoordination Personality changes Irritability slow movements Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 4, 2020 on www.thecalgaryguide.com

AAA-Pathogenesis

Abdominal Aortic Aneurysm (AAA): Pathogenesis Different parts of the aorta have different embryologic origins Atherosclerosis Hypertension Age > 65 Progressive deterioration of aorta structural integrity over life span Connective Tissue Disease Structurally abnormal protein or protein organization in aorta Autoimmunity Infection (e.g Chlamydia, Mycoplasma pneumoniae, Helicobacter pylori, human cytomegalovirus, herpes simplex virus) Antigens (substance that causes immune response) on virus or bacteria resemble local proteins in abdominal aorta Antibodies produced in response to infection inappropriately target host cells in the aorta Antibodies tag cells in the abdominal aorta for destruction by T-lymphocytes Immune-mediated destruction of aorta Smoking Genetics Unclear mechanisms Subacute (not clinically detectable) inflammation of aortic tissue Inflammatory cytokines are released and immune cells are recruited ↑ pressure on aorta and other vessel walls Infiltration of vessel wall by lymphocytes and macrophages Production of enzymes that break down elastin & collagen proteins (which provide most tensile strength to aorta) Aorta susceptible to damage Degradation of aortic connective tissue Biomechanical stress on vessels Authors: Olivia Genereux Davis Maclean Reviewers: Jason Waechter* Amy Bromley* Yan Yu* *MD at time of publication The exact mechanisms are complex, debatable, and an area of intensive research – the 3 mechanisms and associated pathophysiology presented here are generally thought to be the main causes of abdominal aortic aneurysms Infrarenal aorta has poorly developed vaso vasorum (dedicated blood supply to vessel wall) Infrarenal aorta relies solely on nutrient diffusion from aortic blood that crosses abdominal aorta Infrarenal aortic wall has fewer “lamellar” units (fibromuscular units) than other regions of the aorta Infrarenal aorta is less elastic & less able to distribute stress Loss of smooth muscle cells & thinning of tunica media Destruction of elastin in tunica media Normal layers of the aortic wall ↓ aortic tensile strength (ability to withstand stretching) Aorta expands and dilates due to internal pressure Tunica Intima (inner-most tissue layer of aorta) Tunica Media (layers of elastic tissue (elastin) and muscle fibers) Adventitia (thin outermost collagenous layer) (longitudinal section) Aortic aneurysms are usually infrarenal (85%) Abdominal Aortic Aneurysm Infrarenal aorta more prone to ischemia and has impaired repair potential Abnormal, irreversible dilation of a focal area of abdominal aorta (area of aorta between diaphragm & aortic bifurcation) to twice the diameter of adjacent normal artery segment Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published February 27, 2021 on www.thecalgaryguide.com

Hypersensitivity-Pneumonitis

Hypersensitivity Pneumonitis: Pathogenesis and clinical findings Authors: Zarrukh Baig, Zaini Sarwar Reviewers: Natalie Morgunov, Sadie Kutz, Laura Byford-Richardson, Ciara Hanly, Yonglin Mai (麦泳琳)*, Kerri Johannson* * MD at time of publication Farming and Compost Farmer’s Lung (Common) Bird and Animal Proteins Bird Fancier’s Lung (Common) Water Contamination and Ventilation Organic antigen identified by dendritic cells Manufacturing and Chemical Workers Grain and Flour Processors Notes: Immune complex - Production of IgG antibodies (Type III hypersensitivity) Cell mediated - Sensitization of helper T cells (Type IV hypersensitivity) • Thereare3typesofhypersensitivity pneumonitis: acute, subacute, chronic • InacuteHP,removalofincitingantigen results in resolution of symptoms within days. *Lymphoplasmocytic interstitial infiltrate with bronchiolocentric distribution on pathology Epithelial injury (exact mechanism unknown) *Organizing pneumonia Dyspnea, tachypnea, and crackles Abbreviations: • HP – Hypersensitivity Pneumonitis • PFT – Pulmonary Function Test ↑ Neutrophils, mast cells, macrophages, CD8+ T cells, & inflammatory cytokines • *TriadofmainfindingsforsubacuteHP Systemic release of cytokines disrupts hypothalamic regulation Fever Macrophages ingest antigens *Poorly formed granulomas on pathology Tissue breakdown from neutrophils activates fibroblasts, which deposit collagen CT: Normal or diffuse ground- glass opacity (acute) Chronic deposition of collagen replaces normal lung parenchyma by scar tissues (Chronic Findings) Neutrophil elastase breaks down lung elastic fibers Tissue destruction of alveolar walls creates larger air spaces CT: Emphysema CT: Honeycombing (End stage Iung disease) Pathology: Advanced interstitial fibrosis PFT: Restrictive pattern ↓FEV1, ↓FVC, and ↓ DLCO Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 1, 2016, updated October 5, 2021 on www.thecalgaryguide.com

Pneumonie: Pathogenese und klinische Befunde

Pneumonie: Pathogenese und klinische Befunde Autoren: Laura Byford-Richardson Rezensenten: *Yan Yu, Sadie Kutz, Natalie Morgunov, *Kerri Johannson Übersetzung: Sarah Schwarz Übersetungsprüfung: Gesche Tallen* *MD zum Zeitpunkt der Veröffentlichung Anmerkungen: • Pathogene können Bakterien, Viren, Pilze oder Parasiten sein • Die Pneumonie ist eine Entzündung der unteren Atemwege (im Gegensatz zur Entzündung der oberen Atemwege z.B. die Bronchitis) und kann unterteilt werden in: Ambulant erworbene, nosokomial (im Krankenhaus) erworbene Pneumonie Die Immunantwort variiert je nach eingedrungenem Erreger (z.B. Pneumokokken verursachen ein lobär betontes, H. influenzae ein interstitiell betontes Entzündungsbild) Rauchen unterdrückt die Funktionsfähigkeit der neutrophilen Granulozyten und schädigt das Lungenepithel Chronische Lungenerkrankungen z.B. COPD, Asthma oder Lungenkrebs zerstören das Lungengewebe und bieten Krankheitserregern mehr Angriffsfläche für Infektionen Durch Immunsuppression z.B. bei HIV, Sepsis, Glucocorticoid- oder Chemotherapie wird die Immunantwort eingeschränkt Systemisch kommt es zu einer inflammatorischen Immunantwort Durch systemische Zytokinfreisetzung wird die hypothalamische Thermoregulation beeinträchtigt Erregersexposition durch Inhalation, Aspiration, Kontakt- oder hämatologische Übertragung Anfällige Person und/oder virulenter Erreger Proliferation des Erregers in unteren Atemwegen und Alveolen Lokal reagiert das Alveolarepithel mit einer Chemokinausschüttung um neutrophile Granulozyten an den Entzündungsort zu mobilisieren LOBÄR betont: Lokal begrenzte Akkumulation von neutrophilen Granulozyten und Plasmaexudat in Alveolen INTERSTITIELL betont: Zelluläre Infiltrate (Immunzellen und Immunzellfragmente) in den Alveolarwänden (zwischen Alveolen und Kapillaren) Fieber Anmerkungen: Schüttelfrost Irritation der Atemwege mit Hustenreiz Flüssige Infiltrate in Alveolen führen zur Schleimbildung Produktiver Husten Das Exudat vermindert die Röntgenstrahlendur chlässigkeit, entzündete Areale erscheinen im Röntgenbild heller/weiß. Verschattung im Röntgen Alveolen sind durch Flüssigkeitsansamml ungen blockiert Verdickung der Alveolarwände, Diffusionsstrecke ↑ Irritation der Alveolarwände mit Hustenreiz Bei ausschließlich interstitieller Infiltration -> Husten ohne Schleimproduktion Trockener Husten • Andere Symptome der Pneumonie sind: Brustschmerzen, Nutzung der Atemhilfsmuskulatur, auskultatorisch Rasselgeräusche, Müdigkeit • Diese Symptome sind jedoch unspezifisch O2 und CO2- Austausch vermindert Hypoxie Periphere & zentrale Chemorezeptoren werden aktiviert, Atemfrequenz ↑ Luftnot Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 26. September 2016 auf www.thecalgaryguide.com

COPD-发病机制

COPD: 发病机制 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: ! 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " title="COPD: 发病机制 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 慢性阻塞性肺疾病 (COPD) 如果出现在气道周围 气流阻塞 肺不能完全排空 气体，气体潴留 于肺泡(肺过度 充气) 总呼气时长大于 正常时长 呼气相延长 肺组织损伤 呼气时，将空气排出肺外 的弹性回缩力↓ 肺不能完全排空气体， 气体潴留于肺泡内 (肺过度充气) 肺容积↑，膈肌紧张 性收缩(膈肌平坦) 呼气时，胸膜腔正压挤压气道 à 气道阻塞↑ 肺泡通气↓ 血液氧合↓ (低 氧血症) 身体组织灌注 量↓ (比如脑、 肌肉) 疲劳; 运动耐量↓ 黏液生成↑ 清除黏液的上皮纤 毛细胞数量↓ (受 气道炎症损伤) 慢性咳嗽伴咳 痰 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 容积较大 的肺需要 更加努力 才能通气 呼吸肌必须 更用力才能 呼吸 听诊闻及狭窄气 道中的湍流气流 呼气喘鸣音 呼吸困难 气促，尤其是劳累 膈肌无法进一步收缩以 产生深呼吸 呼吸浅快 为了呼吸， 胸壁必须延 展得更大 桶状胸 晚期病人: 患者试图在较高的口 慢性疲劳导致 患者动用辅助呼吸肌和膈肌呼吸， 腔内气压下进行呼气， 活动耐量下降 从而使气道更开放 以改善气流 晚期病人:膈肌 “平坦” ，持续吸气进一步压 缩膈肌à 向内拉季肋部胸壁 胡佛征 (吸气时，胸廓下侧季肋部内收) 缩唇呼吸 肌肉无力 & 消瘦 端坐呼吸 (调动胸肌) 颈部肌肉收 缩(胸锁乳 突肌、斜角 肌) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Findings on Investigations Chronic Obstructive Pulmonary Disease (COPD) Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication Airflow obstruction Lung tissue damage ↓ ventilation of alveoli Blood perfusing ill- ventilated alveoli does not receive normal amounts of oxygen During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction) No elastic recoil to push air out of lungs Loss of lung parenchyma and vasculature ↓ surface area for gas exchange ↓ diffusion capacity (on spirometry) Hypoxemia: PaO2 < 70mmHg (on ABGs) Abbreviations: • FEV1: Forced expiratory volume in 1 second • FVC: Forced vital capacity • TLC: Total lung capacity • VC: Vital Capacity Investigations for COPD : • Spirometry (Pulmonary function test) Total expiration time takes longer than normal FEV1/FEV < 0.7 (on spirometry) Lungs don’t fully empty More air trapped within lungs (hyperinflation) More CO2 remains and diffuses into the blood Hypercapnia: PaCO2 > 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " />

COPD-临床表现

COPD: 临床表现 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: ! 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " title="COPD: 临床表现 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 慢性阻塞性肺疾病 (COPD) 如果出现在气道周围 气流阻塞 肺不能完全排空 气体，气体潴留 于肺泡(肺过度 充气) 总呼气时长大于 正常时长 呼气相延长 肺组织损伤 呼气时，将空气排出肺外 的弹性回缩力↓ 肺不能完全排空气体， 气体潴留于肺泡内 (肺过度充气) 肺容积↑，膈肌紧张 性收缩(膈肌平坦) 呼气时，胸膜腔正压挤压气道 à 气道阻塞↑ 肺泡通气↓ 血液氧合↓ (低 氧血症) 身体组织灌注 量↓ (比如脑、 肌肉) 疲劳; 运动耐量↓ 黏液生成↑ 清除黏液的上皮纤 毛细胞数量↓ (受 气道炎症损伤) 慢性咳嗽伴咳 痰 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 容积较大 的肺需要 更加努力 才能通气 呼吸肌必须 更用力才能 呼吸 听诊闻及狭窄气 道中的湍流气流 呼气喘鸣音 呼吸困难 气促，尤其是劳累 膈肌无法进一步收缩以 产生深呼吸 呼吸浅快 为了呼吸， 胸壁必须延 展得更大 桶状胸 晚期病人: 患者试图在较高的口 慢性疲劳导致 患者动用辅助呼吸肌和膈肌呼吸， 腔内气压下进行呼气， 活动耐量下降 从而使气道更开放 以改善气流 晚期病人:膈肌 “平坦” ，持续吸气进一步压 缩膈肌à 向内拉季肋部胸壁 胡佛征 (吸气时，胸廓下侧季肋部内收) 缩唇呼吸 肌肉无力 & 消瘦 端坐呼吸 (调动胸肌) 颈部肌肉收 缩(胸锁乳 突肌、斜角 肌) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Findings on Investigations Chronic Obstructive Pulmonary Disease (COPD) Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication Airflow obstruction Lung tissue damage ↓ ventilation of alveoli Blood perfusing ill- ventilated alveoli does not receive normal amounts of oxygen During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction) No elastic recoil to push air out of lungs Loss of lung parenchyma and vasculature ↓ surface area for gas exchange ↓ diffusion capacity (on spirometry) Hypoxemia: PaO2 < 70mmHg (on ABGs) Abbreviations: • FEV1: Forced expiratory volume in 1 second • FVC: Forced vital capacity • TLC: Total lung capacity • VC: Vital Capacity Investigations for COPD : • Spirometry (Pulmonary function test) Total expiration time takes longer than normal FEV1/FEV < 0.7 (on spirometry) Lungs don’t fully empty More air trapped within lungs (hyperinflation) More CO2 remains and diffuses into the blood Hypercapnia: PaCO2 > 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " />

adult-pneumonia-pathogenesis-and-clinical-findings

Adult Pneumonia: Pathogenesis and clinical findings Author: Laura Byford-Richardson Reviewers: Tara Shannon, *Yan Yu, Sadie Kutz , Natalie Morgunov, *Kerri Johannson, *Julie Carson *MD at time of publication Smoking à suppressed neutrophil function and damaged lung epithelium Chronic lung conditions e.g. COPD, asthma, lung canceràdestroys lung tissue and offers pathogen more niduses for infection Immune suppression e.g. HIV, sepsis, glucocorticoids, chemotherapyà suppression of immune response Systemic inflammatory response towards invading microbe Systemic cytokine release leads to a disruption in hypothalamic thermoregulation Exposure to a pathogen via inhalation, aspiration, contiguous Notes: or hematological mechanism Susceptible host and/or virulent pathogen Proliferation of microbe in lower airways and alveoli Local response by alveolar epithelial cells release chemokines into surrounding tissue to recruit neutrophils to the site of inflammation • Pathogens can be bacteria, viruses, fungi and parasites • Pneumonia is a lower respiratory tract infection (in contrast to upper respiratory tract infections such as bronchitis) and can be further classified by location of exposure: community, health- care, hospital acquired Inflammatory response varies depending on type of invading pathogen (i.e. S. Pneumonia causes a lobar pattern and Influenza A & B cause an interstitial pattern) LOBAR: Accumulation of neutrophils and plasma exudate from capillaries into alveoli specific to a lung area/lobe INTERSTITIAL: Accumulation of infiltrates (i.e. inflamed cellular debris) in the alveolar walls (i.e. space between the alveolar spaces and bloodstream) Fever Notes: • Other signs and symptoms of pneumonia exist such as chest pain, accessory muscle use, crackles on auscultation and fatigue • These signs and symptoms are less specific to the ones outlined on this slide Irritation and attempted clearance of airways Fluid infiltrates are inside alveoli, airway clearance leads to phlegm production Productive Cough Fluid build up does not allow X-rays to pass through à white opacity on plain film at site of fluid buildup Consolidation on CXR Alveolar sacs blocked by fluid accumulation Thickening of alveolar walls ↑ diffusion distance between alveoli & capillaries Irritated alveolar walls trigger cough reflex Since fluid infiltrates are NOT in the alveoli, attempts to empty the alveoli through coughing doesn’t lead to production of fluid Dry Cough Chills/Rigors ↓ Exchange of CO2 and O2 Hypoxemia Triggers peripheral and central chemoreceptors to ↑ respiratory drive Dyspnea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 26 2016, updated Feb 9, 2022 on www.thecalgaryguide.com

成人肺炎发病机制和临床表现

成人肺炎:发病机制和临床表现

postpartum-puerperal-fever-pathogenesis-and-complications

Postpartum (Puerperal) Fever: Pathogenesis and complications Author: Lindey Felske Reviewers: Brianna Ghali Ran (Marissa) Zhang Ingrid Kristensen* * MD at time of publication Breast Feeding Delayed gastric emptying in pregnancy ↑ Risk of aspiration during delivery Inhalation of gastric contents Chemical burn of the airways from gastric acid Tissue injury Chemokines released by alveolar cells recruit neutrophils Accumulation of neutrophils and plasma exudate in alveoli Aspiration Pneumonia Delivery (Vaginal or Cesarean Section) Tissue damage: Urinary tract catheterization Foreign body can: Introduce bacteria into bladder Provide a biofilm surface for bacterial adhesion Cause mucosal irritation Invasion of bacteria into urinary tract mucosa • • • • Perineal tear/episiotomy (perineal incision) Abdominal incision site Uterine damage Retained products of conception (RPOC) Bacteria enter open tissue Production of antimicrobial peptides and proinflammatory mediators in epidermis Cellulitis Necrosis of RPOC (good medium for bacterial growth) Post-operative pain Hypoventilation from shallow breathing Low volume in alveoli Alveolar collapse Endogenous cervicovaginal flora migrate into the uterine cavity Infiltration of bacteria into endometrium Endometrial TLR4 receptors recognize the endotoxin of Gram-negative bacteria Secretion of proinflammatory cytokines (IL-6, IL-8) and prostaglandin E(2) Activation of coagulation cascade Coagulation in areas of hemostasis (e.g., deep veins) Deep vein thrombosis Dislodged DVT travels to pulmonary arteries Pulmonary embolism • • • Skin openings in breasts (milk ducts +/- cracks) Bacteria from skin and/or saliva enter body Milk backup from blocked duct or poor breastfeeding technique Milk stasis provides environment for bacterial growth Upregulation of IFN- γ, and IL-12A cytokines in milk ducts Mastitis Collection of inflammatory exudate Breast abscess Cytokine expression and inflammatory cell infiltration Sloughing of urinary tract lining to reduce bacterial load Atelectasis Maternal fever (> 38.0°C) within 6 weeks of delivery Urinary tract infection Endometritis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 4, 2022 on www.thecalgaryguide.com The image part with relationship ID rId4 was not found in the file.

Epilepsy Pathogenesis

Epilepsy: Pathogenesis Genetic susceptibility Angelman syndrome, Fragile X syndrome, Tuberous sclerosis, neurofibromatosis Chromosomal abnormalities cause abnormal neural patterns Neural Cerebral palsy, focal cortical dysplasia Malformation of cortical development Cerebrovascular Intracranial hemorrhage, ischemic stroke Other Acquired Head trauma, cerebral infection (i.e., HSV1, VZV, cysticercosis) Neoplasm Metabolic Inborn errors of metabolism Inherited enzyme deficiencies Neurodegenerative Alzheimer’s Disease Protein-rich plaque build-up and brain atrophy Inflammation and formation of scar tissue irritates neural tissue Infiltration of mass, grey matter irritation Damage to the brain and subsequent alteration of neuronal circuitry Neurotransmitter imbalances (i.e. ↑ glutamate, ↓ GABA, ↓ serotonin, ↓ dopamine, ↓ noradrenaline) Abbreviations: • HSV1 – Herpes Simplex Virus 1 • VZV – Varicella Zoster Virus ↑ Inflammatory cytokines (e.g. interleukin-6, tumor necrosis factor-α) Altered neurogenesis and gliosis Ion channel and receptor dysfunction causes imbalance of ion channel charges Authors: Keerthana Pasumarthi Christopher Li Reviewers: Negar Tehrani, Ephrem Zewdie, Ran (Marissa) Zhang, Carlos R. Camara-Lemarroy* * MD at time of publication Neurons fire in burst activity (referred to as paroxysmal depolarization shift) and often in groups (hypersynchrony) Abnormal neural activities eventually create self-reinforcing circuits and transform neural network over time Injuries from falls, bumps, operating heavy machinery Involuntary contractions Loss of consciousness Post-ictal confusion Recurrent seizures Sudden Unexplained Death of Epilepsy Patient (SUDEP) Loss of airway reflexes Aspiration of saliva or food contents Aspiration Pneumonia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 5, 2022 on www.thecalgaryguide.com

exudative-pleural-effusions-pathogenesis-and-lab-findings

Exudative Pleural Effusions: Pathogenesis and Lab Findings Authors: Sravya Kakumanu Reviewers: Ben Campbell *Tara Lohmann * MD at time of publication Chylothorax Damage to thoracic duct Leakage of lymphatic fluid into pleural space Pulmonary embolism Clot obstructs blood flow to lung Infarcted lung tissue Lung infection (e.g. pneumonia, tuberculosis) Lung infection signals inflammatory response Systemic Lupus Rheumatoid Erythematosus (SLE) arthritis (RA) Autoimmune antibodies localize to pleura Pleural tumors (primary or secondary from metastatic cancer) Inflammatory cells migrate to affected site and release cytokines ↑ Permeability of pleural capillaries ↑ Fluid leakage across capillaries Exudative Pleural Effusion Cancer invades lymphatic drainage of pleural space (PS) ↓ Drainage of pleural fluid (PF) from pleural space If infectious etiology Tumor invasion = inflammatory response See Pleural Effusions: X-ray Findings and Physical Exam Findings of Lung Diseases slides ↑ Permeable pleural capillaries allow ↑ protein and cell leakage into pleural space If pleural tumour: Release of cancer cells into pleural space Cancer cells on PF cytology 60-75% sensitive for malignancy If rheumatoid arthritis: Release of auto-antibodies into pleural space Auto-antibodies initiate inflammatory response in pleural space ↑ Inflammatory cells have ↑ glucose metabolism in pleural space Sterile PF with mildly elevated white blood cells, normal pH, normal glucose ↑ Inflammation at infection site damages endothelium of pleura Pleural Infection Stage I: Simple Parapneumonic Effusion ↑ Inflammatory cells and bacterial cells in pleural space have ↑ glucose metabolism in pleural space Bacterial invasion from infected parenchymaà pleural space < 40mg/dL glucose in PF ↑ Activation of coagulation cascade and ↓ fibrinolytic activity ↑ Deposition of fibrin clots/membranes within pleural space creates loculated effusion (compartmentalized effusion due to septations in pleural space) ↑ Production of lactate dehydrogenase (LDH) (LDH maintains NAD+ supply during ↑ glucose metabolism) ↑ CO2 production pH of PF < 7.20 ↑ CO2 production pH of PF < 7.20 < 3.3mmol/L glucose in PF Pleural Infection Stage II: Complicated Parapneumonic Effusion Loculated effusion OR bacteria present OR ↓ pH + ↓ glucose ↑ Fibroblast proliferation creates thickened pleura ↑ Pus in pleural space Pleural Infection Stage III/Empyema: Loculated effusion and pus in pleural space PF/serum protein ratio ≥ 0.5 PF/serum LDH ratio ≥ 0.6 Light’s Criteria: Any criteria can be met to be an exudative pleural effusion PF LDH ≥ 2/3 upper limit of normal Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 9, 2022 on www.thecalgaryguide.com

ventilator-associated-pneumonia-pathogenesis-and-clinical-findings

Ventilator-Associated Pneumonia: Pathogenesis and Clinical Findings Respiratory failure or inability Risk factors: e.g. immunocompromised, poor swallowing to maintain airway ability, weakened respiratory muscles, chronic disease Insertion of endotracheal tube (ETT) for invasive mechanical ventilation to maintain respiration Paralytics and sedatives lead to inhibition of cough reflex Damage to cilia on epithelial cells of trachea during insertion of ETT ↓ Mucociliary clearance Insertion of nasogastric (NG) tube for feeding Constant opening by NG tube ↓ esophageal sphincter function Introduction of oropharyngeal microbes during intubation Severe acute illness impairs phagocytosis and dysregulates T- cells (mechanism unclear) Medications, chronic disease, or severe acute illness can weaken immune system Desensitization of pharyngoglottal adduction reflex (PAR) (PAR normally induces closure of epiglottis to protect the airway when swallowing) ↑ Reflux of gastric contents Accumulation of subglottic secretions containing microbes Microbial colonization on inside of ETT Development of biofilm on inside of ETT Dislodgement of biofilm into lower airway ↑ Age or chronic disease can weaken respiratory function Micro aspirations of subglottic and gastric contents Impaired mechanisms to remove microbes from airway Positive pressure pushes microbes down Fever/rigors ↑ White blood cell count Introduction of pathogenic microbes to airway Susceptible patient (not required for infection) Septic shock See Distributive Shock slide Sepsis Microbes descend airway and infect lungs Ventilator-Associated Pneumonia (VAP) Occurs > 48-72 hours after intubation ↑ Inflammatory response at infection site promoting immune cell extravasation and cytokine release Cytokine signalling ↑ permeability of capillaries leading to ↑ fluid leakage into interstitium and alveoli Authors: Sravya Kakumanu Reviewers: Ben Campbell *Tara Lohmann *Bryan Yipp * MD at time of publication Acute respiratory distress syndrome See ARDS pathogenesis slide Pleural effusion Lung consolidation on chest x-ray (CXR) ↑ Sputum production to clear fluid on CXR (Note: In patients with Acute Respiratory Distress Syndrome (ARDS), look for VAP consolidation in non- within alveoli/airways (may be Positive microbial culture from sputum dependent/upper regions of the lung where ARDS consolidation would be unexpected to extend to) purulent in worse infections) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 2, 2022 on www.thecalgaryguide.com

chest-exam-findings-of-lung-pleural-diseases

Chest Exam Findings of Lung & Pleural Diseases Note: Please see slides on pathogenesis of Transudative and Exudative Pleural Effusions, Primary and Tension Pneumothorax, Adult Pneumonia, Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), Heart Failure, and Kidney Disease Authors: Sravya Kakumanu Reviewers: Ben Campbell, *Tara Lohmann, *Yan Yu * MD at time of publication Interstitial Lung Disease Pneumothorax Rupture of visceral pleura Build-up of air within pleural space Pleural Effusion Atelectasis Consolidation ↑ Hydrostatic pressure pushes fluid into pleural space ↑ Capillary permeability = fluid leaks into pleural space ↓ Oncotic pressure = fluid moves into pleural space Bronchus obstructed Scarring/infiltration of lung tissue Surfactant dysfunction (ex. ARDS) Loss of contact between visceral and parietal pleura (ex. effusion, pneumothorax) Parenchymal compression (ex. loculated effusion, mass) ↑ Hydrostatic pressure pushing fluid into alveoli (ex. cardiogenic pulmonary edema) ↑ Capillary permeability allowing fluid to move into alveoli (ex. pneumonia) Idiopathic Connective tissue diseases Sarcoidosis, Amyloidosis Chronic medical diseases (ex. COPD, heart failure, kidney disease, etc) Occupational or environmental exposures (ex. silicosis, organic dusts, metals, gases, aerosols, etc) Accumulation of fluid in pleural space Collapse of alveoli Accumulation of fluid within alveoli Pulmonary fibrosis (scarring of alveoli bilaterally) Breath Sounds Lung unable to inflate fully Fluid in pleural space Collapsed lung unable to inflate Airspace filled with fluid and unable to fill with air dampens sound ↓ Breath sounds ipsilaterally Scarred alveoli unable to expand to fill with air ↓ Breath sounds bilaterally (may not be noticeable) Chest Rising on Inspiration Chest cavity filled with air, but lung Lung unable to inflate fully Scarred alveoli unable to expand to fill with air unable to inflate fully ↑ Chest size, ↓ Rising ipsilaterally ↓ Chest rising ipsilaterally ↓ Chest rising bilaterally (may not be noticeable) Percussion Sound resonates through air in pleural space Ipsilateral hyperresonance on percussion Sound unable to resonate through pleural fluid Sound unable to resonate through compacted lung tissue Ipsilateral dullness on percussion Sound unable to resonate through fluid-filled alveoli Diffuse scarring of alveoli No notable changes on percussion Tracheal Deviation Air pushes trachea Fluid pushes trachea ↓ Pressure within chest wall pulls trachea No pushing or pulling of trachea Contralateral tracheal deviation Ipsilateral tracheal deviation No tracheal deviation Adventitious Lung Sounds Alveoli not impacted (i.e. not collapsed or fluid-filled) Sudden opening of collapsed alveoli filling with air Fine inspiratory crackles Air movement through fluid-filled alveoli Coarse inspiratory crackles Fluid-filled alveoli can’t dampen breath sounds from larger central airways Bronchial breath sounds all over consolidated area (harsh, ↑ pitch with expiratory phase > inspiratory; only normal when heard centrally over trachea + bronchi) Scarred inelastic alveoli suddenly open on inspiration Fine inspiratory crackles No crackles No abnormal breath sounds Severe pneumothorax or effusion pushing against lung parenchyma Other sounds Amplification of patient voice through fluid-filled alveoli Tactile fremitus (↑ vibrations felt by hand placed on chest wall when patient speaks) *Whispers also sound louder on auscultation Fluid-filled alveoli only allow certain sound frequencies to be audible Egophony (“E” sounds like “A” on auscultation) Legend: Pathophysiology Mechanism Physical Exam Findings Complications Published October 9, 2022 on www.thecalgaryguide.com

Coronary Artery Bypass Graft CABG Indications

Coronary Artery Bypass Graft (CABG): Indications Author: Breanne Gordulic Reviewers: Miranda Schmidt Ben Campbell Sunawer Aujla Angela Kealey* * MD at time of publication Symptomatic multivessel (≥ 3 vessels) coronary artery disease (MVCAD) or complex MVCAD Acute coronary syndrome (ACS) Left main coronary artery disease Multivessel (≥ 3 vessels) CAD and diabetes Cardiac surgery required for other pathology Multivessel CAD, LV dysfunction and congestive heart failure (CHF) Complex CAD includes stenosed vein grafts, bifurcation lesions, calcified lesions, total occlusions, ostial lesions STEMI initial treatment is PCI/thrombolysis CABG outcomes compared to percutaneous coronary intervention (PCI) in MVCAD include ↑ survival in diabetes, ↑ survival with LV dysfunction, ↓ repeat revascularization, ↓ myocardial infarction, ↓ stroke ↑ Risk of failure in complex CAD with PCI Rapid reperfusion to myocardium most important in STEMI to decrease myocardial damage CABG can be considered for residual stenoses 6-8 weeks later NSTEMI or unstable angina (UA) with MVCAD involving at least three vessels including the proximal left anterior descending (LAD) Left main coronary artery divides into left anterior descending (LAD) and left circumflex (LCx) which supplies 2/3 of myocardium ↑ Survival Myocardial infarction from left main artery occlusion Death Left main stenosis Ventricular dysrhythmias Ongoing ischemia LV dysfunction Hemodynamic instability ↑ risk of PCI CABG has mortality benefit ↓ Number of operations ↑ Risk of cardiovascular disease in diabetes Revascularization indicated along with other cardiac surgery Multivessel CAD with >90% stenosis and CHF LV ejection fraction <35% ↑ Risk of atherosclerosis from hyperglycemia and dyslipidemia CABG bypasses several atherosclerotic plaques in coronary arteries ↑ Durability ↑ Complete perfusion Valve stenosis or regurgitation Septal defect Aortic root or arch pathology Combination procedure Evidence of ischemia at rest Evidence of impaired LV function at rest ↓ All-cause mortality in CABG vs medical management Chronic obstructive pulmonary disease Abbreviations: • ACS- acute coronary syndrome. Acute reduction in blood flow to heart muscle resulting in cell death. • CAD- coronary artery disease. Narrowing or blockage of the coronary arteries by plaque • NSTEMI- myocardial infarction (heart attack) with no ST elevation on electrocardiogram • PCI- percutaneous coronary intervention. A balloon tipped catheter is used to open blocked coronary arteries; a stent may be placed. • STEMI- myocardial infarction with ST segment elevation on electrocardiogram Consider revascularization (restore blood flow to blocked or narrowed blood vessels) of coronary arteries to increase perfusion to myocardium (heart muscle) Coronary artery bypass graft recommended Assess surgical risk and comorbidities with evaluation by heart team that includes both a cardiac surgeon and interventional cardiologist (SYNTAX Trial) Individual management plan for patients with comorbidities that increase mortality Frailty Chronic Renal Failure ↑ Inflammation and deregulated angiogenesis affects all organ systems ↓ Physiologic reserve and ↓ ability to recover from acute stress ↑ Pneumonia ↑ Respiratory and Renal Failure ↑ Stroke ↑ In hospital mortality ↓ Survival two years after surgery Use Society of Thoracic Surgeons Score, EuroSCORE, or SYNTAX II Score to predict patient outcome with anatomy, disease severity, and preoperative characteristics Coronary Artery Bypass Graft Surgery to take healthy blood vessels from the body and connect them proximally and distally to blocked coronary arteries Cardiopulmonary bypass, fluid overload, ↑ renal vasoconstriction and ↓ renal oxygenation from rewarming Kidney injury ↑ End stage kidney disease Blood flow restored to ischemic myocardium ↓ Angina ↑ Quality of life ↑ LV function ↑ Survival Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 12, 2023 on www.thecalgaryguide.com

Acute Laryngitis

Acute Laryngitis: Pathogenesis and clinical findings Infectious Author: Charmaine Szalay-Anderson Reviewers: Shayan Hemmati, Sunawer Aujla, Derrick Randall*, Viral (most common) Malaise Fever Fungal Atopy (asthma, allergy) Non-infectious Gastroesophageal Reflux Trauma or damage to larynx Smoking Yan Yu* * MD at time of publication Environmental Pollution/Inhalants Bacterial (S. pneumoniae, H. influenzae, M. catarrhalis) Systemic immune response Spread of infection to larynx through upper respiratory tract Infection of the vocal folds and surrounding tissue Mechanical (vocal misuse/ trauma) (Area in the neck that contains the structures for voice production, anatomically anterior to the esophagus, inferior to the pharynx and superior to the trachea) Irritation of the vocal folds and surrounding tissue Inflammatory cascade triggered Acute Laryngitis Symptoms for <3 weeks Acute injury to vocal folds Vocal fold lesions (i.e., vocal polyps) Laryngeal inflammation Neutrophils and macrophages release inflammatory cytokines Local laryngeal inflammationà↑ vascular permeability ↑ Secretion of mucous leading to airway congestion Cough reflex initiated to clear airway congestion Cough Edema of vocal folds and surrounding tissue Dysphagia (difficulty swallowing) Dysphonia (difficulty speaking) Odynophagia (painful swallowing) Swelling impairs vocal cord vibration Frank aphonia (loss of voice) Progressive worsening of edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 24, 2023 on www.thecalgaryguide.com

Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome: Pathogenesis and clinical findings Acute respiratory distress syndrome (ARDS) is a clinical syndrome involving acute lung injury. It results in severe hypoxemia and bilateral Authors: David Olmstead Mao Ding Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson* * MD at time of publication ↓ PaO2 (Partial pressure of oxygen in arterial blood ↓SpO2 (Peripheral oxygen saturation) Tachypnea (↑ RR) Tachycardia (↑ HR) Dyspnea Bilateral Opacity on chest radiograph ↓ PaO2, ↓SpO2 ↑ PaCO 2 ↑ PaO2, ↓PaCO2 Eupnea (normal breathing) ↓ O2 Requirements Depression, Anxiety, PTSD Neuromuscular Weakness Chronic Respiratory Dysfunction airspace disease in the absence of elevated left-heart pressures. Direct Lung Injury Causes include pneumonia and pulmonary sepsis (community- acquired, hospital-acquired, aspiration, viral), drowning, and chemical pneumonitis from aspiration or direct inhalational injury Indirect Lung Injury Causes include sepsis with a non-pulmonary source, trauma, severe burns, transfusion- related acute lung injury (TRALI) and pancreatitis Lung Tissue Inflammation Exudative: Neutrophils migrate into the alveoli in response to inflammatory stimulus Note: While the three phases of ARDS take place in sequence, all areas of the lung may not be in the same phase at the same time. For this reason, the processes can be thought of as overlapping. Proliferative: Body attempts to heal damage. If it is not successful, the tissue transitions to the fibrotic phase Neutrophil-containing pulmonary exudate interferes with surfactant function Neutrophil infiltration and proinflammatory cytokines lead to tissue edema, dysfunction and subsequent destruction of pulmonary epithelium Residual debris in alveoli are cleared by phagocytic cells Restoration of alveolar epithelial cells. Alveoli collapse in absence of working surfactant Damaged epithelium impairs gas exchange Pulmonary capillaries do not adequately absorb fluid The body’s attempts to heal lung tissue result in deposition of hyaline membranes in the alveoli Ventilation- Perfusion Mismatch Pulmonary Edema Impaired Gas Diffusion Functional epithelium is able to absorb fluid back into circulation ↑ useful surface area for gas exchange Clearing of CXR Impaired Function After Prolonged Illness Pulmonary Hypertension Fibrotic: Inadequate healing results in long-term pulmonary damage (rare) Fibroblast activity leads to deposition of collagen in alveoli and alveolar capillaries Fatigue Pulmonary Fibrosis Nail Clubbing (nails appear wider & swollen) Cough/Dyspnea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 6, 2018, updated Oct 10, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome: Note: Acute respiratory distress syndrome is a clinical Authors: David Olmstead Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson* * MD at time of publication Pathogenesis and clinical findings Direct Lung Injury Causes include pneumonia and pulmonary sepsis (community-acquired, hospital-acquired, aspiration, viral), drowning, and chemical pneumonitis from aspiration or direct inhalational injury Indirect Lung Injury syndrome involving acute lung injury. It results in severe hypoxemia and bilateral airspace disease in the absence of elevated left-heart pressures. Causes include sepsis with a non-pulmonary source, trauma, severe burns, transfusion-related acute lung injury (TRALI) and pancreatitis Lung Tissue Inflammation Exudative: Neutrophils migrate into the alveoli in response to inflammatory stimulus Note: While the three phases of ARDS take place in sequence, all areas of the lung may not be in the same phase at the same time. For this reason, the processes can be thought of as overlapping. Proliferative: Body attempts to heal damage. If it is not successful, the tissue transitions to the fibrotic phase Neutrophil-containing pulmonary exudate interferes with surfactant function Neutrophil infiltration and proinflammatory cytokines lead to tissue edema, dysfunction and subsequent destruction of pulmonary epithelium Abbreviations: PaO2: Partial pressure of oxygen in arterial blood SpO2: Peripheral oxygen saturation. CXR: Chest radiograph. Residual debris in alveoli are cleared by phagocytic cells Restoration of alveolar epithelial cells. Alveoli collapse in absence of working surfactant Damaged epithelium impairs gas exchange Pulmonary capillaries do not adequately absorb fluid The body’s attempts to heal lung tissue result in deposition of hyaline membranes in the alveoli Ventilation- Perfusion Mismatch Pulmonary Edema Impaired Gas Diffusion ↓ PaO2, ↓SpO2 Tachypnea Tachycardia Dyspnea Bilateral Opacity on CXR ↓ PaO , ↓SpO 2 2 ↑ PaCO2 ↑ PaO2, ↓PaCO2 Eupnea ↓ O2 Requirements Clearing of CXR Depression, Anxiety, PTSD Neuromuscular Weakness Chronic Respiratory Dysfunction ↑ useful surface area for gas exchange Functional epithelium is able to absorb fluid back into circulation Impaired Function After Prolonged Illness Fibrotic: Inadequate healing results in long-term pulmonary damage (rare) Fibroblast activity leads to deposition of collagen in alveoli and alveolar capillaries Pulmonary Fibrosis Pulmonary Hypertension Cough/Dyspnea Nail Clubbing Fatigue Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 06, 2018 on www.thecalgaryguide.com

Pneumonia Pediatri Patogenesis dan Temuan klinis

Pneumonia Pediatri: Patogenesis dan Temuan klinis

Guillain-Barre Syndrome

Guillain-Barré Syndrome: Pathogenesis and clinical findings Author: Nissi Wei Mao Ding Reviewers: Owen Stechishin Matthew Harding Cory Toth* * MD at time of publication ↑ Protein in cerebrospinal fluid (CSF) Minor triggers surgery, trauma, bone marrow transplant Initiate immune response (unknown mechanism) GI/respiratory infection (1-3 weeks prior) Campylobacter jejuni, cytomegalovirus, HIV, Epstein-Barr Virus Molecular mimicry: shared ganglioside antigens between peripheral nerve and pathogen coat proteins IgG antibodies to ganglioside antibodies in serum Nerve Conduction Study : ↓ conduction velocity, conduction block Triggered immune response cross-reacts with peripheral nerves, beginning at nerve roots ↑ permeability of blood- nerve barrier at level of proximal nerve roots Demyelination: antibodies attack Schwann cells secondary damage Axonal damage: antibodies attack nodes of Ranvier Nerve Conduction Study: ↓ CMAP (compound muscle action potential) amplitude, normal conduction velocity Acute inflammatory demyelinating polyneuropathy (AIDP) (80-90%) Acute motor axonal neuropathy (AMAN) Acute motor sensory axonal neuropathy (AMSAN) Acute immune-mediated polyneuropathy Tachycardia & Dysrhythmias (Needs cardiac monitoring) Sudden Death Dysautonomia: disruption of the autonomic nervous system responsible for involuntary functions Sensory deficits Motor deficits Universal Areflexia (loss of deep tendon reflexes) Phrenic nerve involvement Diaphragm paralysis Cranial Nerve (CN) involvement Bulbar palsy (CN IX, X, XI,XII) Oculomotor weakness (CN III, IV, VI) Eye Movement Abnormalities (Miller Fisher Syndrome – rare form of regionally- restricted AIDP) BP Fluctuation/ Orthostatic Hypotension (drop of blood pressure from seated/lying to standing) Urinary Retention (transient, late-course) Limb Weakness (legs usually affected first) Impaired swallowing àaspiration pneumonia ↓ ability to clear airway secretions Pain & Paresthesia (in back and extremities) Respiratory Failure (Life threatening: needs ventilatory observation and possibly support) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 1, 2013, updated Oct 15, 2023 on www.thecalgaryguide.com Guillain-Barré Syndrome Minor triggers (surgery, trauma, GI/respiratory infection Campylobacter jejuni, CMV, HIV , EBV (1-3 weeks prior) Molecular mimicry: shared ganglioside antigens between peripheral nerve and pathogen coat proteins Author: Nissi Wei Reviewers: Owen Stechishin Matthew Harding Cory Toth* * MD at time of publication ↑ Protein in CSF bone marrow transplant) Initiate immune response (unknown mechanism) IgG antibodies to ganglioside antibodies in serum NCS: ↓ conduction velocity, conduction block Triggered immune response cross-reacts with peripheral nerves, beginning at nerve roots ↑ permeability of blood- nerve barrier at level of proximal nerve roots NCS: ↓ CMAP amplitude, normal conduction velocity Demyelination: antibodies attack Schwann cells secondary damage Axonal damage: antibodies attack nodes of Ranvier Acute inflammatory demyelinating polyneuropathy (AIDP) (80-90%) Acute motor axonal neuropathy (AMAN) Cranial nerve involvement Dysautonomia Acute motor sensory axonal neuropathy (AMSAN) Eye Movement Abnormalities (Miller Fisher Syndrome – rare form of regionally-restricted AIDP) Acute immune-mediated polyneuropathy Oculomotor weakness (CN III, IV, VI) Bulbar palsy (CN IX, X, XI,XII) Phrenic nerve involvement ↓ ability to clear airway secretions Impaired swallowingà aspiration pneumonia Diaphragm paralysis Respiratory Failure (Life threatening: needs ventilatory observation and possibly support) Motor deficits Sensory deficits Pain & Paresthesias in back and extremities Limb Weakness (legs usually affected first) Universal Areflexia Urinary Retention (transient, late-course) Sudden Death BP Fluctuation, Orthostatic Hypotension Tachycardia, Dysrhythmias (Needs cardiac monitoring) Abbreviations: • NCS - nerve conduction study • CMAP - compound muscle action potential • EBV - Epstein-Barr Virus • CMV - cytomegalovirus • CN - cranial nerve Note: Aα, Aβ peripheral nerve fibres (large, fast-conducting, heavily myelinated axons for muscle stretch, light touch & proprioception) are more affected than Aδ and C fibres (small, less myelinated, slowly-conducting fibres for pain and temperature) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 1, 2013 on www.thecalgaryguide.com

Death Cardiovascular Respiratory and Neurologic Mechanisms

Death: Cardiovascular, Respiratory and Neurologic Mechanisms Mitochondria in tissues unable to utilize O2 Reduced hemoglobin in blood to carry O2 Low oxygen content in blood (CaO2) Hypoxemia (Type I Respiratory Failure): low dissolved oxygen in blood (PaO2) Lungs can’t oxygenate blood fast enough Lungs can’t rid blood of CO2 fast enough Hypercapnia / hypercarbia (Type II Respiratory Failure): elevated dissolved CO2 in blood (PaCO2) Cerebral vasodilation Toxins: e.g. cyanide, pesticides, arsenic Severe anemia Distributive problems: Systemic inflammation (sepsis, anaphylaxis, pancreatitis), adrenal insufficiency, vasodilatory drugs Obstructive problems: Cardiac tamponade*, tension pneumothorax* or massive pulmonary embolism* Hypovolemic* problems (low blood volume): Hemorrhage, dehydration, widespread skin disruption or burns Cardiac valve dysfunction Myocardial infarction* or cardiomyopathy Cardiac arrhythmia or heart block Disturbed electrical activity in cardiomyocytes Peripheral metabolic disturbances Hypokalemia*, Hyperkalemia* Acidosis* (including renal failure) Hypothermia* Toxins* (e.g. cocaine, beta blockers, tricyclics) Severe thyroid derangement Inappropriate systemic vasodilation Adjacent forces impair heart filling Low cardiac preload Low stroke volume (SV; depends on valves, contractility, preload) Decreased systemic vascular resistance (SVR) Low blood pressure (BP = CO x SVR) Decreased cardiac output (CO = SV x HR) Disseminated intravascular coagulationàwidespread thrombi that occlude blood flow (also causes hemorrhage, see relevant box at left) Methemoglobinemia: some hemoglobin gets stuck in a state that can’t carry O2 Hemoglobin has reduced capacity to carry or release O2 Drugs: e.g. dapsone, nitrates Carbon monoxide poisoning Circulatory collapse / shock: inadequate perfusion of tissue with blood Respiratory collapse: blood has insufficient useable O2 content Ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) Hypoxia*: inadequate O2 delivery or utilization in tissues Hypoxia creates metabolic disturbances that impair cardiac cells. Alternatively, any of the preceding conditions marked with (*) can directly trigger cardiac arrest first Pulseless Electrical Activity (PEA): organized activity on ECG with no cardiac output (can be preceded or mimicked by pseudo-PEA, in which there is still some output on ultrasound) Low atmospheric pressure or oxygen content Severe lung disease Asthma, COPD, interstitial lung disease, congestive heart failure, pulmonary hypertension, pulmonary embolism, lung collapse / atelectasis Acute respiratory distress syndrome Pneumonia, aspiration pneumonitis, inhalational injury, systemic inflammation, drowning Severe hypoventilation Respiratory fatigue, advanced COPD, chest wall disorders, neuromuscular disorders, upper airway obstruction, toxins (e.g. opioids, botulism) Can degenerate at any time Asystole: no cardiac electrical activity or output Death Respiratory arrest: cessation of breathing Inability to protect airway Decreased level of consciousness Note This is a broad overview of the many scenarios that can result in death. For detailed explanations of the various disease mechanisms, refer to the corresponding slides. * = reversible causes of cardiac arrest (Hs and Ts) Author: Ben Campbell Reviewers: Yan Yu* Huma Ali* * MD at time of publication Bradycardia (low heart rate, HR) Unopposed parasympathetic stimulation of heart (can also cause vasodilation, see Distributive problems) Disruption of spinal cord sympathetic control Injury to cervical or upper thoracic spinal cord Irreversible cessation of cardiac, respiratory, and brain function Prolonged seizure initially causes increased cardiovascular activity, until the system fatigues Disruption of respiratory control center in medulla Expanding skull contents squeeze brainstem (herniation) Increased intracranial pressure Edema from intracranial hemorrhage, trauma, brain mass Edema, inflammation, hypoxia and/or metabolic derangements cause diffuse neuron dysfunction Central nervous system infection Dementia, particularly with delirium Massive ischemic stroke Seizure activity prevents or alters breathing Metabolic disturbances that affect the central nervous system Hypoglycemia Hypocalcemia, hypercalcemia Hyponatremia, hypernatremia Uremia Acute liver failure (hyperNH4) Many drugs / toxins Withdrawal (e.g. EtOH) Status epilepticus Brainstem lesion (e.g. stroke, neoplasm, inflammatory) Nervous System Insult Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 11, 2023 on www.thecalgaryguide.com Respiratory System Insult Cardiovascular System Insult Cardiogenic problems

Mechanical Ventilation mechanisms of action and complications

Mechanical Ventilation: Mechanisms of Action and Complications Authors: Madison Amyotte Reviewers: Victória Silva, Mao Ding Eric Leung* * MD at time of publication Mechanical ventilation is a form of life support that helps a patient breathe (ventilate) when they cannot breathe on their own. Invasive: Delivery of positive pressure to the lungs via endotracheal or tracheostomy tube Mechanical ventilation Pressure support ventilation (PSV): Set inspiratory pressure & flow. Patient initiates all breaths unassisted Non-invasive: Delivery of oxygen into the lungs via positive pressure through the mouth No endotracheal or tracheostomy tube Assist/control ventilation (AC): Set respiratory rate & tidal volume (amount of air delivered to the lungs with each breath). Patient can trigger additional assisted breaths Synchronized intermittent mandatory ventilation (SIMV): Set tidal volume & respiratory rate. Patient can trigger additional unassisted breaths 02 mask delivery Continuous positive airway pressure (CPAP) Provides continuous positive ventilatory pressure Bilevel positive airway pressure (BIPAP) Provides positive pressure with two different pressure levels for inhalation and exhalation ↑ Swallow non- inspiratory flow Aspiration Acute rise in airway pressure Barotrauma Patient- triggered breath Ventilator senses negative pressure from inflation of the lungs Time-triggered breath Respiratory rate set at x breaths per min Patient-triggered breath Ventilator senses negative pressure from inflation of the lungs Tidal volume determined by patient’s strength & lung compliance Time-triggered breath Respiratory rate set at x breaths per min Delivery of set tidal volume, inspiratory flow rate & pattern Complete patient- triggered breaths Ventilator senses negative pressure from inflation of the lungs Breathes assisted by set inspiratory pressure Inspiratory flow drops below set inhalational negative pressure threshold Pressure support terminates as exhalation cycle begins Combined with SIMV Inspiratory pressure added to patient triggered breaths Patient can overcome resistance of the endotracheal tube or ↑ volume of spontaneous breathes Delivery of set tidal volume, inspiratory flow rate & pattern Airways remain open & clear of obstruction Forced air into nasal passages Nose bleeds (epistaxis) Maximum tidal volume reached Exhale valve opens Patient exhales actively or passively until set end expiratory pressure in the lungs is reached (PEEP) to prevent alveolar collapse Patient exhales until PEEP reached Patient achieves optimal ventilation throughout respiratory cycles Mouth breathing Dry mouth (xerostomia) Increased work of breathing & muscle fatigue Prolonged weaning & extubation Breath stacking ↑ Volume and pressure in lungs Lung tissue injury (barotrauma) Microorganisms colonize artificial airway Ventilator associated pneumonia if ventilation >48 hrs Tachypnea ↓ CO2in circulation Respiratory alkalosis Legend: Pathophysiology Mechanism Sign/symptom/lab finding Complications Published Nov 25, 2023 on www.thecalgaryguide.com

Aspiration Pneumonia

Aspiration Pneumonia: Pathogenesis and clinical findings Intractable vomiting ↑ Likelihood of oropharyngeal and gastric contents exiting the esophagus, entering the trachea to the lung If the acidic gastric contents are sterile, then aspirating this results in inflammation and lung injury without development of infection Aspiration pneumonitis Alveolar macrophages recruit neutrophils to local site of infection. Subsequent cytokine release compromises the vascular endothelial cell wall barrier and ↑ alveolar-capillary permeability ↑ inflammation due to fluid and cellular debris build-up in alveoli overdose (e.g. opioids) (e.g. stroke) Altered level of consciousness and impaired cough/clearance Tube Poor Alcohol and Substance Medications Neurologic diseases Esophageal and gastric motility disorders Impaired swallowing Chronic obstructive pulmonary disorder feeding oral health Bacteria adhere to epithelial surfaces and ↑ risk of airway and lung bacterial colonization Aspirated oropharyngeal and gastric contents can also contain bacteria ↓ Elimination and clearance of foreign bacteria from airway and lung Macroaspiration (large volume aspiration) of oropharyngeal bacteria, during eating and drinking Bacteria and fluid fill bronchi and alveolar space Aspiration Pneumonia Alterations to lung microbial flora An infectious lung process caused by inhalation of foreign bacterial and oropharyngeal and gastric contents Aspiration of acidic fluid and pneumonia causative pathogen (typically anaerobes or bacteria in normal oral flora) with resultant inflammation Infiltrate develops in a gravity-dependent pattern in patches around bronchi segments. Produces proinflammatory cytokines, (e.g. tumor necrosis factor-alpha, and interleukin-1) Hypothalamic production of prostaglandin E2 results in thermogenesis Fever Authors: Luiza Radu Reviewers: Mao Ding, *Yan Yu, *Jonathan Liu *MD at time of publication Aspiration to the right lung more common due to large diameter and more vertical orientation of the right main bronchus Crackles and ↑ lung vibrations (fremitus) on auscultation Productive Cough Impaired alveolar gas exchange Chemoreceptor detection of ↓ pO2 triggers ↑ ventilation Hypoxemia Dyspnea Consolidation in lower lobes (particularly superior segments) and posterior segments of upper lobes If untreated, a pus-filled lung cavity develops (e.g. abscess) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 11, 2024 on www.thecalgaryguide.com

Epiglottitis

Epiglottitis: Pathogenesis and clinical findings Infectious cause: Bacterial (Staphylococcus aureus, Streptococcus pneumoniae, Neisseria meningitidis, or most commonly Haemophilus influenzae in unimmunized children), viral or fungal Authors: Alisha Ebrahim Reviewers: Simran Sandhu Mao Ding Michelle J. Chen Danielle Nelson* * MD at time of publication Infectious agent invades the bloodstream and/or the epithelial layer of the epiglottis, aryepiglottic folds and adjacent structures, allowing for spread Non-infectious cause: Ingestion of toxin or foreign body, thermal injury, or trauma The potential space between the squamous epithelial layer and the epiglottal cartilage fills with inflammatory cells such as neutrophils and eosinophils Exudate of inflammatory cells spreads through the lymphatic and blood vessels in the lingual surface of the epiglottis and periepiglottic tissues Fluid and inflammatory cells accumulate between the squamous epithelial layer and epiglottal cartilage Swelling of the entire supraglottic larynx Tripod/sniffing position (Anxious- looking and sitting with trunk leaning forward, neck hyper-extended and chin pushed forward to maximize airway diameter) Stridor (High-pitched sound that is produced by obstruction in the larynx or just below) Stertor (Low-pitched noise created in the nose or the back of the throat) Retraction of the intercostal and suprasternal muscles Tachypnea (Rapid breathing) Increased weight and mass of the epiglottis Epiglottis curls posteriorly and inferiorly Ball-valve effect (Airflow obstructed during inspiration as epiglottis is pulled over airway but not during expiration as epiglottis moves back into position) ↓ Diameter of upper airway Epiglottis obstructs the esophagus Dysphagia (Difficulty swallowing) Cyanosis (Blue tint to skin) Turbulent inspiratory airflow Aspiration of oropharyngeal secretions Hypoxemia (Low oxygen levels in blood) ↓ Air entry to lungs Airway obstruction ↑ Work of breathing Drooling Pain when swallowing Muffled/”hot potato” voice Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 5, 2024 on www.thecalgaryguide.com

Sickle Cell Disease Pathogenesis Clinical Findings and Complications

Sickle Cell Disease: Pathogenesis, Clinical Findings, and Complications DNA point mutation in chromosome 11 causes a substitution of glutamate to valine for the sixth amino acid of the β-globin chain Authors: Yang (Steven) Liu Priyanka Grewal Reviewers: Alexander Arnold Luiza Radu JoyAnne Krupa Yan Yu* Lynn Savoie* * MD at time of publication Hemoglobin S (HbS) variant formed instead of normal Hemoglobin A (HbA) Hb electrophoresis shows approximately 45% HbS, 52% HbA (ααββ), 2% HbA Hb electrophoresis shows approximately 90% HbS, 8% HbF, & 2% HbA . No HbA present (ααδδ), & 1% HbF (ααγγ;2 fetal hemoglobin) Heterozygous: point mutation in one of the two chromosomes (Hb AS) Sickle cell trait (asymptomatic unless severely hypoxic) Homozygous: point mutation in both chromosomes (Hb SS) Sickle cell disease An inherited blood disorder characterized by defective hemoglobin that leads to red blood cells sickling 2 Dehydration Hypoxemia Acidosis ↓ Volume of RBC cytoplasm ↓ O2 Saturation of Hb O morereadily 2 released from Hb in low pH environment ↑ Concentration of deoxygenated HbSinred blood cells (RBCs) Hydrophilic glutamate→ hydrophobic valine substitution makes HbS less soluble in the cytoplasm & more prone to polymerization & precipitation in its deoxygenated state ↑ Concentration of deoxygenated Hb in RBC leads to ↑ polymerization rate Polymerized & precipitated HbS forms long needle-like fibers RBC shape becomes sickled Sickle cells on peripheral blood smear Vaso-occlusion (sickled RBCs lodge in small vessels, blocking bloodflow to organs & tissues) Blockage of venous outflow Occlusion of vessels in lungs ↑ pulmonary blood pressure Fluid extravasates into interstitial tissue leading to pulmonary edema Acute chest syndrome (chest pain, hypoxemia (↓blood oxygen), etc.)** to the penis: to the spleen: Priapism (persistent, painful erection) Splenic Sequestration (blood pools in spleenà splenomegaly & hypotension) Extravascular hemolysis (macrophages in the spleen phagocytose sickled RBCs) Normocytic anemia ↑Marrow erythropoiesis (RBC production) to compensate for hemolysis Infarction of bone Pain crises If occurring in hands Dactylitis (inflammation of digits) Blockage of arteries ↓ oxygenation of organs & tissues Vaso-occlusion of the splenic artery Splenic infarction (↓ blood supply leads to tissue death) RBC inclusions (structures found in RBCs) not removed by spleen Howell-Jolly bodies (RBC DNA remnants) on blood smear Vaso-occlusion of other arteries (cranial, renal, etc) Stroke, renal failure ↑ RBC breakdown ↑ Unconjugated bilirubin released from RBC breakdown RBC precursors (reticulocytes) are released into the blood stream Reticulocytosis (increased number of immature red blood cells) on peripheral blood smear Patient’s RBC level becomes dependent on increased marrow activity Bone marrow infarction or viral infections (i.e. Parvovirus B19) suppresses bone marrow activity Aplastic crises (profound anemia) ** See corresponding Calgary Guide slide(s) ↑ Serum level of unconjugated bilirubin Some of the circulating unconjugated bilirubin deposits in the skin Jaundice (yellowing of skin) ↑ Conjugation of bilirubin in liver ↑Amounts of conjugated bilirubin released into bile Gallstone formation Cholelithiasis (presence of gallstones in the gallbladder) Spleen releases invasive encapsulated bacteria (eg. Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis) into circulation, which causes infections Meningitis Sepsis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 16, 2013, updated Apr 29, 2024 on www.thecalgaryguide.com

Acute Otitis Media Pathogenesis and Clinical Findings in Children

Acute Otitis Media in Children: Pathogenesis and clinical findings Congenital conditions (e.g. Down Syndrome, Pierre Robin syndrome) Exposure to tobacco smoke Impaired macrophage function in nasopharynx Lack of immunizations Lack of breastfeeding Infant does not receive antibodies from breast milk Overcrowding Age 6 – 16 months Immune system deficiencies Close proximity of kids & ↓ sanitation (e.g. daycare) ↑ Infection risk Upper Respiratory Tract Infection (i.e. bacterial (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis), viral) Immature Eustachian tube anatomy which facilitates pathogen transmission to middle ear Author: Jody Platt Stephanie de Waal Reviewers: Yan Yu Elizabeth De Klerk William Kim Annie Pham Michelle J. Chen Danielle Nelson* * MD at time of publication Abnormal anatomical structure (e.g. cleft palate) ↑ Nasopharyngeal streptococcus pneumoniae Lack of immunity to pathogens ↑ Colonization of nasopharynx with bacterial pathogens Inflammation & edema of respiratory mucosa including the nose, nasopharynx, and Eustachian tube Obstruction of the Eustachian tube Air from middle ear resorbs into circulation which creates a low-pressure environment Negative pressure gradient pulls viral/bacterial pathogens into middle ear Degenerating white blood cells, tissue debris, and microorganisms accumulate & develops into purulent effusion Inflammation & infection of middle ear Complications of acute otitis media** ↑ Pressure in middle ear Stretching of tympanic membrane Helper T cells & macrophages release cytokines into the bloodstream Cytokines trigger hypothalamus to ↑ thermoregulatory set-point Effusion behind tympanic membrane Effusion obstructs visualization of ossicles Neutrophils infiltrate middle ear & phagocytose pathogens Pus accumulates behind the tympanic membrane Blood vessels of the tympanic membrane vasodilate Bulging tympanic membrane Otalgia (ear pain) Discomfort disrupts daily activities in young children Fever Irritable Poor feeding Tympanic membrane erythema Painful blisters on tympanic membrane (e.g. Bullous myringitis) Can persist for up to 3 months after infection resolves Loss of tympanic membrane landmarks (i.e. handle of malleus, light reflex) ** See corresponding Calgary Guide slide Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 28, 2013; updated Aug 25, 2024 on www.thecalgaryguide.com

Pediatric Pneumonia Pathogenesis and Clinical Findings

Pediatric Pneumonia: Pathogenesis and clinical findings Authors: Jasmine Nguyen Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Annie Pham Eric Leung* Jean Mah* * MD at time of publication Immunological: unvaccinated, primary immunocompromise, pre-existing illness (e.g. HIV, measles), malnutrition Environmental: smoke, air pollution, mold, crowded housing Recent hospitalization or antibiotic-use Physiological: neonates, low-birth weight, underlying lung disease These factors make the host more susceptible to infection Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to infection/proliferation of microbial pathogens at the alveolar level Exposure to pathogen via inhalation, hematogenous, direct exposure, or aspiration Epithelial cells in respiratory tract release cytokines that recruit neutrophils & plasma proteins to infection site, initiating a local inflammatory response Cytokines released into the bloodstream (e.g. TNF, IL-1) initiate a systemic inflammatory response ↑ Vascular permeability Accumulation of exudate, cellular debris, serous fluid, fibrin, or bacteria in the airway spaces ↑ Respiratory drive Tachypnea ↑ Excitability of the peripheral somatosensory system Circulating cytokines induce prostaglandin synthesis Airway irritation as cilia are unable to efficiently clear fluid buildup Crackles, ↓ breath sounds Fluid, protein, or inflammatory cells leak into pleural space Pleural effusion Pulmonary edema Fluid buildup in interstitial spaces ↑ gas diffusion distance Bacteria enter the bloodstream (if bacterial pneumonia) Sepsis Fluid buildup in the alveoli ↓ available surface area for gas diffusion ↓ Efficiency of gas exchange Intra- and extracranial arteries dilate Headache ↑ Thermo-regulatory set-point of the hypothalamus Fever Myalgia Hypoxemia Malaise Cough Fluid accumulation in the pleural space prevents full lung expansion ↑ Work of breathing (tracheal tug, paradoxical abdominal breathing, subcostal/suprasternal indrawing) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 28, 2018; updated Aug 25, 2024 on www.thecalgaryguide.com Pediatric Pneumonia: Pathogenesis and clinical findings Authors: Jasmine Nguyen Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Annie Pham Eric Leung* * MD at time of publication Immunological: unvaccinated, primary immunocompromise, pre-existing illness (e.g. HIV, measles), malnutrition Environmental: smoke, air pollution, mold, crowded housing Recent Hospitalization: length of stay, recent antibiotics, mechanical ventilation Physiological: neonates, low-birth weight, underlying lung disease (ciliary dysfunction, asthma, cystic fibrosis, bronchiectasis) Host is more susceptible to infection Exposure to pathogen: inhalation, hematogenous, direct, aspiration Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to infection/proliferation of microbial pathogens at the alveolar level Notes: • Additional findings in pediatric pneumonia may include increased irritability, nausea/vomiting, diarrhea, otitis, and headache • Viral pathogens most common in children <2yrs; bacterial pathogens most common in children >2yrs Local inflammatory response: epithelial cells release cytokines in response to infection, which recruit neutrophils and plasma proteins to site of infection ↑ Vascular permeability causes accumulation of plasma exudate, cellular debris, serous fluid, fibrin, or bacteria in the airway spaces Systemic inflammatory response: Cytokine release (eg. TNF, IL-1) ↑ respiratory drive Airway irritation as cilia are unable to efficiently clear fluid buildup Crackles, ↓ breath sounds Fluid, protein, or inflammatory cells leak into pleural space Pleural effusion Pulmonary edema Fluid buildup in interstitial spaces increases gas diffusion distance Fluid buildup in the alveoli decreases available surface area for gas diffusion ↓ efficiency of gas exchange Bacteria invade into the bloodstream (if bacterial pneumonia) Sepsis Hypoxemia Circulating cytokines induce prostaglandin synthesis, which raise the thermoregulatory set-point of the hypothalamus paradoxical abdominal breathing, subcostal/suprasternal indrawing) Fever Cough Fluid accumulation in the pleural space prevents full lung expansion, resulting in ↓ lung volumes Tachypnea ↑ Work of breathing (tracheal tug, Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Month Day, Year on www.thecalgaryguide.com Pediatric Pneumonia: Pathogenesis and clinical findings Immunological: immunization status, immune compromise Environmental: second-hand smoke, air pollution Hospitalization: length of stay, recent antibiotics, mechanical ventilation Neonates, immunocompromise, underlying lung disease (ciliary dysfunction, Cystic Fibrosis, bronchiectasis) Authors: Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Eric Leung* * MD at time of publication Additional findings in pediatric pneumonia may include nausea, otitis, headache Viral pathogens most common in children <2yrs; bacterial pathogens most common in children >2yrs Interstitial pattern: suspect Mycoplasma pneumoniae, Influenza A + B, Parainfluenza Lobar pattern: suspect S. pneumonia, H. influenzae, Moraxella, S. aureus Systemic inflammatory response: Cytokine release (eg. TNF, IL-1) Exposure to pathogen: inhalation, hematogenous, direct, aspiration Susceptible host and/or virulent pathogen Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to proliferation of microbial pathogens at the alveolar level Notes: • • • • Local inflammatory response: neutrophils recruited to site of infection (LOBAR or INTERSTITIAL PATTERN, depending on pathogen) by epithelial cytokine release Irritation of contiguous structures and/or referred pain (mechanism unclear) Acute abdominal pain Cough Accumulation of plasma exudate (from capillary leakage at sites of inflammation), cell-debris, serous fluid, bacteria, fibrin ↑ respiratory drive Disruption of hypothalamic thermoregulation Fever/chills Irritation of airways and failure of ciliary clearance to keep up with fluid buildup Crackles, ↓ breath sounds Fluid buildup in spaces between alveoli (INTERSTITIAL PATTERN) Interstitial opacity on CXR Fluid buildup in alveoli (LOBAR PATTERN) ↓ efficiency of gas exchange (↑ diffusion distance in INTERSTITIAL, ↓ surface area in LOBAR) Hypoxemia Tachypnea Lobar consolidation on CXR Respiratory accessory muscle use (chest indrawing, paradoxical breathing, muscle retractions) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 28, 2018 on www.thecalgaryguide.com gin