Entire semester Together Flashcards
What is an allergy?
A heightened sensitivity to a foreign protein called an allergen, elicited through ingestion, contact, or inhalation.
Define rhinitis.
Eosinophilic inflammation of the nasal mucosa and paranasal sinuses resulting from an IgE-mediated reaction.
List the manifestations of allergic rhinitis.
- Nasal congestion
- Obstructed airflow
- Increased mucous production
- Drainage
What is the initial phase of allergic rhinitis onset in atopic individuals?
Sensitization followed by subsequent reexposure to a designated allergen.
What role do antigen-presenting cells play in allergic rhinitis?
They assimilate a low-dose exposure of the antigen and present it to helper T lymphocytes.
What cytokines are produced by activated helper T lymphocytes?
- IL-4
- IL-5
- IL-13
What triggers mast cell activation in allergic rhinitis?
The binding of specific antigens to IgE antibodies affixed to mast cells.
What are the hallmark acute symptoms of allergic rhinitis?
- Rhinorrhea
- Nasal congestion
- Nasal irritation
- Sneezing
What is the role of histamine in allergic rhinitis?
Stimulates sensory nerve endings of the Vth nerve, eliciting sneezing and prompts mucous gland secretion.
When does the late phase response of allergic rhinitis occur?
4-6 hours after antigen stimulation.
What is the duration of symptoms in the late phase of allergic rhinitis?
Symptoms can last for about 18-24 hours.
What cells predominantly infiltrate the affected area during the late phase?
- T lymphocytes
- Basophils
- Eosinophils
What is the significance of cytokines in the late phase response?
They orchestrate the release of mediators and facilitate the infiltration of inflammatory cells.
What are some well-known risk factors for allergic rhinitis?
- Atopy
- Asthma
- Eczema
- Other allergies
How does parental history factor into allergic rhinitis risk?
A parental history of allergic rhinitis, asthma, and pollen allergies is a documented risk factor.
What are common food allergens that cause allergic rhinitis in infancy and childhood?
- Milk
- Eggs
- Soy
- Wheat
What role does the gut microbiota play in allergic disease pathogenesis?
The composition of the gut microbiota influences immune function and may play a role in allergic diseases.
List the four main classes of microbiomes.
- Bacteroidetes
- Actinobacteria
- Firmicutes
- Proteobacteria
What is dysbiosis?
An imbalance in gut microbiota associated with atopy and allergic disorders.
How can dysbiosis affect allergic rhinitis?
It can disrupt Th1/Th2 homeostasis, affecting immunotolerance and increasing the risk of allergic rhinitis.
Fill in the blank: Probiotics may be one of the options clinicians may use to improve their patients’ quality of life since treating AR is _______.
[challenging]
What is the gut microbiome diversity in allergic rhinitis (AR) patients?
Reduced gut microbiome diversity
Increased Bacteroidetes; decreased Actinobacterium, Proteobacterium, and Escherichia coli.
What are potential biomarkers associated with allergic rhinitis?
Increased:
* S. Shigella
* E. coli
* Parabacteroides
* Lachnoclostridium
* Dialister
Decreased:
* Oxalobacter
* Clostridiales
These markers indicate shifts in microbial populations in AR patients.
Which microbiome metrics are observed in AR patients?
Lower diversity indices (Chao1 and Shannon)
* More abundant Bacteroidetes
* Reduced Firmicutes
How is symptom severity linked to gut microbiome composition in AR?
Symptoms linked to levels of Butyrococcus and Eisenbergiella
What are common symptoms of allergic rhinitis?
- Clear and watery nasal discharge
- Nasal congestion
- Postnasal drip
- Itching of the nose, throat, and eyes
What physical examination findings are consistent with allergic rhinitis?
- Mouth breathing
- Frequent sniffling/throat clearing
- Transverse supra-tip nasal crease
- Allergic shiners (dark circles under the eyes)
What findings are observed during anterior rhinoscopy in AR patients?
- Swelling of the nasal mucosa
- Thin, clear secretions
- Bluish hue of inferior turbinates
- Cobblestoning of the nasal mucosa
What is seasonal allergic rhinitis?
Symptoms can occur or increase due to pollination of specific plants
What triggers perennial allergic rhinitis?
- Dust mites
- Animal dander
- Mold spores
- Cockroaches
- Food allergens
- Infection
- Nonspecific irritants
What are the classifications of allergic rhinitis based on symptom frequency?
- Intermittent: < 4 days/week or < 4 weeks’ duration
- Persistent: > 4 days/week or > 4 weeks’ duration
What are common complications of allergic rhinitis?
- Adenoid hypertrophy
- Eustachian tube dysfunction
- Chronic rhinosinusitis
- Nasal polyps
- Sleep disruption
- Learning disturbances
What are the symptoms of nonallergic rhinitis?
- Nasal obstruction
- Clear rhinorrhea
- Sneezing and itchy, watery eyes are not common
What characterizes viral rhinitis?
Accompanied by other viral illness symptoms like headaches, malaise, body aches, and coughing
What is occupational rhinitis?
Caused by exposure to indoor and outdoor pollutants like dust, ozone, and cigarette smoke
What is vasomotor rhinitis?
A common form of nonallergic rhinitis triggered by environmental conditions
What is the primary neurotransmitter involved in mucus secretion during vasomotor rhinitis?
Acetylcholine
What is nonallergic rhinitis with eosinophilia (NARES)?
A syndrome with nasal obstruction and congestion, severe exacerbations, and marked eosinophilia (> 25%)
What causes rhinitis medicamentosa?
Overuse of topical nasal decongestants like oxymetazoline and phenylephrine
What physiological changes occur during pregnancy that contribute to nasal congestion?
- Increased estrogen levels
- Increased hyaluronic acid in nasal tissue
- Decreased nasal cilia
- Increased mucous glands
What are some systemic diseases that can cause chronic rhinosinusitis?
- Granulomatosis with polyangiitis
- Aspirin-exacerbated respiratory disease (AERD)
- Cystic fibrosis
- Immunodeficiency
- Primary ciliary dyskinesia
What defines chronic rhinosinusitis (CRS)?
Inflammation of the nasal cavity and paranasal sinuses lasting more than 12 weeks
What are common clinical features of chronic rhinosinusitis?
- Purulent drainage
- Facial/dental pain
- Nasal obstruction
- Hyposmia
- Headaches
- Fatigue
What are the signs of infection severity in sinusitis?
Fever is an important indicator despite having only 50% sensitivity
What findings should be observed during nasal endoscopy for sinusitis diagnosis?
- Purulent drainage
- Polyps
- Polypoid changes in the mucosa
- Edema or erythema
What are nasal polyps?
Benign inflammatory and hyperplastic growths from the sinonasal mucosa
They usually arise from the lateral nasal wall or the ethmoid recess.
Where do nasal polyps typically appear?
In the nose or sinuses
What types of cells are found in nasal polyps?
- Plasma cells
- Lymphocytes
- Eosinophils
- Mucous glands
What is the primary cause of nasal polyps?
T-helper 2 (Th2) cell-driven eosinophilia and IgE inflammation
What factors can contribute to the formation of nasal polyps?
- Allergic environment
- Age-related anatomical changes
- Impaired clearance of irritants
What are common clinical features of nasal polyposis?
- Nasal obstruction
- Facial congestion
- Decreased sense of smell
- Rhinorrhea
What examination techniques are used to diagnose nasal polyposis?
- Anterior rhinoscopy
- Nasal endoscopy
What is the nasal septum?
A wall composed of osteocartilaginous tissue that separates two nasal cavities
What can asymptomatic minor deviations of the nasal septum indicate?
Normal developmental variations
What conditions can nasal septal deviation lead to?
- Headaches
- Rhinosinusitis
- Obstructive sleep apnea
What is acute pharyngotonsillitis commonly caused by?
Viruses (most common) or bacteria
What are common symptoms of acute pharyngotonsillitis?
- Fever
- Malaise
- Odynophagia
- Dysphagia
- Foul breath
What percentage of acute pharyngotonsillitis cases are caused by viral infections?
Approximately 70 to 85%
Which viruses are common pathogens in acute pharyngotonsillitis?
- Adenoviruses
- Rhinoviruses
- Coronaviruses
- Epstein-Barr viruses
- Cytomegaloviruses
- Coxsackieviruses
- Herpes simplex viruses
- Influenza viruses
What is a hallmark symptom of Epstein-Barr virus (EBV) infection?
Lymphoid hypertrophy, especially in posterior nodes
What is acute retroviral syndrome associated with HIV?
A manifestation that can cause pharyngitis
What is the main cause of acute bacterial pharyngotonsillitis in children?
Group A beta-hemolytic streptococcus (GABHS)
What are the complications associated with acute streptococcal pharyngotonsillitis?
- Scarlet fever
- Acute rheumatic fever
- Poststreptococcal glomerulonephritis
- Pediatric autoimmune neuropsychiatric disorder associated with GABHS
What symptoms are associated with scarlet fever?
- Erythematous rash
- Fever
- Lymphadenopathy
- Dysphagia
- Erythematous tonsils
What is a peritonsillar abscess?
A consequence of infection spreading from the superior pole of the tonsil
What pathogens commonly cause peritonsillar abscess?
- GABHS
- Staph aureus
- Haemophilus influenza
- Prevotella
- Porphyromonas
- Fusobacterium
What are the clinical presentations of peritonsillar abscess?
- Severe pain
- Odynophagia
- Muffled voice
- Dysphagia
What can cause parapharyngeal space abscesses?
Infections from peritonsillar abscesses or tonsils spreading through the superior constrictor muscle
This abscess is located between the superior constrictor muscle and the deep cervical fascia.
What symptoms can result from parapharyngeal abscesses?
Trismus and decreased neck range of motion due to inflammation of adjacent muscles
The tonsil and pharyngeal walls may be displaced medially.
What happens if a parapharyngeal abscess is untreated?
It can spread down the carotid sheath into the mediastinum.
What is a retropharyngeal abscess?
An infection in the lymph nodes of the retropharyngeal space or from a peritonsillar abscess
More common in children.
What are the symptoms of a retropharyngeal abscess?
Fever, dysphagia, muffled speech, noisy breathing, stiff neck, cervical lymphadenopathy
What type of streptococci can cause Non-Group A Streptococcal Pharyngitis?
Group C and G streptococci
How does Non-Group A Streptococcal Pharyngitis compare to Group A?
Similar presentation but usually less severe symptoms
What causes pharyngeal diphtheria?
Corynebacterium diphtheriae
What characterizes the disease caused by Corynebacterium diphtheriae?
A grayish, tightly adherent pseudomembrane covering tonsils and extending to nares, uvula, soft palate, and pharynx
What is a potential risk associated with diphtheria?
Airway compromise and cardiac/neurotoxicity from exotoxins
Which pathogens can cause tonsillar infections related to sexually transmitted diseases?
Neisseria gonorrhoeae and Treponema pallidum
What is a common presentation of gonococcal infections?
Exudative pharyngitis
What are the symptoms of primary oral syphilis?
Painless chancre on lips, buccal mucosa, or oropharynx
What can occur in secondary syphilis patients?
Oropharyngeal and tonsillar ulcers and bilateral tonsillar hypertrophy
What causes oropharyngeal candidiasis?
Overgrowth of Candida albicans
What do the plaques of oropharyngeal candidiasis resemble?
White cottage cheese-like plaques
What characterizes recurrent acute tonsillitis?
Recurrent episodes of acute tonsillitis with complete recovery between episodes
What is the typical bacterial flora in children with recurrent tonsillitis?
Polymicrobial, including Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae
What defines chronic tonsillitis?
Sore throat lasting at least three months, tonsillar inflammation, halitosis, and tender cervical adenopathy
What are tonsilloliths?
Microbial biofilms that form within tonsillar crypts
What can cause aphthous ulcers?
Human herpesvirus 6, although this remains uncertain
What are the characteristics of minor aphthous ulcers?
Smaller than 1 cm in diameter and heal in 10-14 days
What conditions can present with large or persistent ulcerative stomatitis?
Erythema multiforme, drug allergies, acute herpes simplex, pemphigus, pemphigoid, epidermolysis bullosa acquisita, bullous lichen planus, Behçet disease, IBD
What is the most common pathogen causing supraglottitis?
Haemophilus influenzae type B (HIB)
What are the clinical features of supraglottitis?
Fever, difficulty breathing, severe odynophagia, drooling, irritability, leaning forward, muffled voice, inspiratory stridor
What is the primary cause of laryngitis?
Viral upper respiratory infections
What are common bacteria involved in bacterial laryngitis?
S pneumoniae, H influenzae, M catarrhalis
What noninfectious causes can lead to laryngitis?
Vocal trauma, inhalation injuries, allergies, gastroesophageal reflux disease, asthma, pollution
What characterizes bacterial tracheitis?
Secondary bacterial colonization following a viral respiratory tract infection
What is the most common pathogen isolated in bacterial tracheitis?
Staphylococcus aureus
What defines obstructive lung diseases?
Impaired ability of air to leave the alveoli during expiration, clinically defined by decreased FEV1/FVC ratio
What are examples of obstructive lung diseases?
- Bronchial Asthma
- Chronic Obstructive Pulmonary Disease
- Chronic Bronchitis
- Emphysema
- Bronchiectasis
What defines restrictive lung diseases?
Reduced total lung capacity and reduced FEV1/FVC ratio
What are examples of restrictive lung diseases?
What characterizes bronchial asthma?
Episodic airway obstruction, airway hyperresponsiveness, and inflammation
What is the heritable predisposition percentage for asthma?
25–80%
What triggers bronchoconstriction in asthma?
- Allergens
- Infections of upper airways
- Inhalatory irritants
- Anxiety
- Cold air
- Physical activity
- Gastroesophageal reflux
- Drugs (e.g., nonsteroidal anti-inflammatory drugs)
What are the two older classifications of asthma?
Extrinsic and intrinsic
What are the two newer classifications of asthma?
Allergic asthma and nonallergic asthma
What is allergic asthma also known as?
Atopic asthma
What is nonallergic asthma also referred to as?
Nonatopic asthma
What are some causes of allergic asthma?
- Pollens
- Dust
- Drugs
What is the mechanism of allergic asthma?
Type I hypersensitivity reaction
Which demographic does allergic asthma occur more frequently in?
Children
What associated conditions may patients with allergic asthma have?
- Hay fever
- Eczema
What triggers nonallergic asthma?
- Exercise
- Cold air
- Drugs
- Gastroesophageal reflux
- Viral infections
What is a hallmark of asthma?
Airway hyperresponsiveness
What are the two components of airway hyperresponsiveness?
- Functional component
- Structural component
What occurs during the early stage of asthma?
Mediators promoting bronchoconstriction
What mediators are involved in the early stage of asthma?
- Leukotrienes C4, D4, and E4
- Histamine
- Prostaglandin D2 (PGD2)
What happens in the late stage of asthma?
Release of enzymes by eosinophils and neutrophils
What is a significant morphological change in asthma?
Smooth-muscle constriction and mucus
What are the pathological features of asthma?
- Airway lumen is reduced
- Thickening of the submucosa
- Edema and cellular infiltration
What is the classic triad of clinical symptoms in asthma?
- Wheezing
- Dyspnea
- Cough (night-time)
What is status asthmaticus?
A prolonged asthmatic attack which can be fatal
What is the definition of Chronic Obstructive Pulmonary Disease (COPD)?
Preventable and treatable disease with airflow limitation that is not fully reversible
What is the most significant risk factor for COPD?
Smoking
What are the four interrelated events in the pathogenesis of COPD?
- Inflammatory and immune cell recruitment
- Proteinases damage the extracellular matrix
- Structural cell death through oxidant-induced damage
- Disordered repair of elastin
What is the typical spirometry finding in late asthma?
Low peak expiratory flow (PEF) and decreased FEV1/FVC
What occurs to arterial blood gases during an exacerbation of asthma?
CO2 is low secondary to hyperventilation
What are eosinophilia and its relevance in asthma?
Increased eosinophils are often associated with asthma inflammation
Fill in the blank: The early stage of asthma is characterized by _______.
[mediators promoting bronchoconstriction]
True or False: Nonallergic asthma is associated with elevated IgE levels.
False
What triggers airway narrowing in asthma?
Continued or additional exposures and triggers
What is the definition of Chronic Bronchitis?
Productive cough for at least 3 months in 2 consecutive years.
What is the pathogenesis of Chronic Bronchitis?
Cigarette smoking – airway irritation - increased production of mucus - hyperplasia of mucous-secreting glands.
What are the types of Chronic Bronchitis?
- Simple
- Obstructive
- Asthmatic
What does the lumen contain in Small Airway Pathology in COPD Chronic Bronchitis?
Mucus and inflammatory debris.
What is Goblet cell metaplasia?
Transformation of airway epithelium to goblet cells, associated with mucus overproduction.
What happens to the submucosal layer in Chronic Bronchitis?
Increased thickness due to an increase in fibrous tissue and inflammatory cells.
What is a key characteristic of Emphysema?
Dilation of airspaces.
What are the histological features of Emphysema?
Loss of pulmonary parenchyma and greatly increased size of the airspaces.
What are the two types of Emphysema?
- Centriacinar emphysema (smoking)
- Panacinar emphysema (α1-antitrypsin deficiency)
What is the definition of Bronchiectasis?
An irreversible airway dilation that involves the lung in either a focal or a diffuse manner.
What are the two components required for the pathogenesis of Bronchiectasis?
- Infection
- Obstruction
What is the difference between focal and diffuse Bronchiectasis?
- Focal: bronchiectatic changes in a localized area of the lung.
- Diffuse: widespread bronchiectatic changes throughout the lung.
What is the ‘Vicious Cycle Hypothesis’ in Infectious Diffuse Bronchiectasis?
Susceptibility to infection leads to chronic inflammation and ongoing propagation of the infectious/inflammatory cycle.
What are common complications of Bronchiectasis?
- Recurrent infections
- Hemoptysis
What are the general characteristics of Restrictive Lung Diseases?
- Acute: ARDS - Diffuse Alveolar Damage
- Chronic: Idiopathic Pulmonary Fibrosis, Sarcoidosis, Pneumoconioses
What characterizes Acute Restrictive Lung Disease?
Disease developing over a short time period (minutes to days) secondary to a major systemic insult.
What is the clinical term for acute restrictive lung disease?
Acute respiratory distress syndrome (ARDS).
What are the stages of Diffuse Alveolar Damage?
- Exudative stage
- Proliferative stage
- Fibrosis
What are the main causes of Diffuse Alveolar Damage?
- Severe pulmonary infection
- Aspiration
- Sepsis
- Severe trauma with shock
What is the pathophysiology of symptoms in Chronic Restrictive Lung Disease?
Chronic diffuse lung injury, inflammation, and fibrosis leading to impaired gas exchange.
What are the histological categories of Idiopathic Interstitial Pneumonia?
- Usual interstitial pneumonia (UIP)
- Nonspecific interstitial pneumonia (NSIP)
- Organising pneumonia (OP)
- Diffuse alveolar damage (DAD)
- Desquamative interstitial pneumonia (DIP)
- Respiratory bronchiolitis (RB)
- Lymphocytic interstitial pneumonia (LIP)
What is the prognosis for Non-Small Cell Lung Cancer?
Accounts for 80% of all lung cancers.
What are the three main subtypes of Non-Small Cell Lung Cancer?
- Adenocarcinoma
- Squamous cell carcinoma
- Large cell carcinoma
What is the most common subtype of lung cancer in North America?
Adenocarcinoma.
What is a characteristic of Squamous Cell Carcinoma?
Characterized histologically by the presence of keratin pearls.
What is the prognosis for Large Cell Carcinoma?
10% 5-year survival.
What is the peak age for lung cancer?
Between 60 and 70 years.
What percentage of lung cancers does Small Cell Lung Cancer account for?
13.8%
Is Small Cell Lung Cancer more common in men or women?
Slightly more common in women
What is Small Cell Lung Cancer strongly associated with?
Smoking
Where is Small Cell Lung Cancer often located?
Centrally or in the hilum
What type of cells do Small Cell Lung Cancers develop from?
Neuroendocrine cells
How does the growth and spread of Small Cell Lung Cancers compare to non-small cell lung cancers?
They grow and spread more quickly
What is the 5-year survival rate for Small Cell Lung Cancer?
5%
What is the single most important predictor of prognosis in lung cancer?
Tumor stage
What does the TNM staging system stand for?
- T: tumor size and extent of local and/or regional spread
- N: spread of tumor to regional or distant lymph nodes
- M: presence of distant metastases or involvement of the pleural fluid
What characterizes Stage I lung cancer?
Small tumor size and absence of lymph node involvement and metastases
What determines Stages II & III of lung cancer?
Extent of regional lymph node involvement
What defines Stage IV lung cancer?
Any tumor with distant metastasis
At initial diagnosis, what percentage of patients have localized lung cancer?
20%
What is the most common presenting symptom of lung cancer?
Cough
In what percentage of cases is lung cancer diagnosed in asymptomatic patients as an incidental finding?
7-10%
What are common clinical features due to the primary tumor in lung cancer?
- Cough
- Hemoptysis
- Dyspnea
- Wheezing
- Atelectasis
- Postobstructive pneumonia
What are the features of Pancoast tumors?
- Shoulder and upper back pain
- Horner’s syndrome
- Severe arm and shoulder pain
What syndrome can occur due to obstruction of the superior vena cava in lung cancer?
Superior vena cava syndrome
What are common symptoms of distant metastasis in lung cancer?
- Weight loss
- Bone pain
- Altered sensation
- Headache
- Jaundice
What are paraneoplastic syndromes?
Clinical syndromes involving nonmetastatic systemic effects that accompany a cancer
What are the two most common causes of paraneoplastic syndromes?
- Production and release of physiologically active substances by the cancer
- Altered immune response
What is hypercalcemia due to in lung cancer?
Ectopic production of a parathyroid hormone related peptide
What is the lifetime risk of developing lung cancer in smokers?
12-17%
What substance in tobacco smoke is known to cause DNA damage?
Polyaromatic hydrocarbons
What is the most common occupational risk factor for lung cancer?
Exposure to asbestos
What percentage of lung cancers are associated with radon exposure?
10%
What are activating mutations in the EGFR gene associated with?
Adenocarcinomas
What is the prognosis for typical carcinoids after surgery?
90% 5-year survival
What type of cancer is mesothelioma?
Cancer of the pleural lining
What is the main cause of mesothelioma?
Asbestos exposure
What percentage of lung cancers are carcinoid tumors?
2-3%
What are the two subtypes of carcinoid tumors?
- Typical carcinoid
- Atypical carcinoid
What is the prognosis for atypical carcinoids after surgery?
60% 5-year survival
What is the mean pulmonary arterial pressure used to diagnose pulmonary hypertension?
> 20 mmHg
What is primary pulmonary hypertension associated with?
Mutations of BMPR2, ALK1, and endoglein
What is the driving pressure in the pulmonary artery?
10 mm Hg
What are the common sites for lung metastasis?
- Edges of the lungs
- Lower lobes
What are common cancers that metastasize to the lung?
- Bladder cancer
- Breast cancer
- Colorectal cancer
- Kidney cancer
- Melanoma
- Sarcomas
- Testicular
What is loose collagen?
Medium-sized vein obliterated by loose connective tissue - an organized thrombus
What is Pulmonary Arterial Hypertension (PAH) WHO Group I?
Primary Pulmonary Hypertension: Rare precapillary disorder caused by increased pulmonary arterial tone
What are the potential causes of idiopathic PAH?
May be idiopathic, hereditary with mutations in BMPR2, ALK1, endoglein, or due to drugs/toxins
What is the effect of drugs or toxins on PAH?
Cause endothelial dysfunction, increase pulmonary arterial tone, promote vascular remodeling, leading to increased PVR
What is idiopathic PAH (IPAH)?
A progressive disease that leads to right heart failure and early mortality
How does the prevalence of IPAH differ between genders?
Women to men by ~3.1-fold; more common in women in their 20s and 30s
How does the prognosis of PAH differ between men and women?
Men have more severe hemodynamics at diagnosis and a less favorable prognosis compared to women
What is the impact of pathologic changes on pulmonary arterial compliance?
Results in a progressive increase in total pulmonary vascular resistance (PVR)
What must increase to preserve cardiac output in PAH?
Right ventricular work must increase
What is a common clinical symptom of PAH?
Insidious onset of dyspnea
What happens in end-stage PAH regarding cardiac output?
CO declines, leading to a decrease in mPAP
What are frequent extrapulmonary vascular manifestations of PAH?
Overactivation of neurohumoral signaling, renal failure, volitional muscle atrophy
What is the typical histological finding in severe pulmonary hypertension?
Plexiform lesions
What is the prognosis for patients with PAH under medical treatment?
5-year survival is about 30%
What treatment is often indicated for PAH?
Heart–lung transplantation
What is the definition of pulmonary edema?
An abnormal accumulation of fluid in the interstitial and alveolar spaces of the lung
Why is pulmonary edema considered an important complication?
It can be life-threatening and occurs in various heart and lung diseases
What are frequent causes of pulmonary edema?
What characterizes interstitial edema?
Increased lymph flow, widened lymphatics, perivascular and peribronchial engorgement
How does alveolar edema affect the lungs?
Fluid moves across the epithelium into the alveoli, preventing ventilation
What are common symptoms of pulmonary edema?
- Difficulty breathing (dyspnea) * Cough producing frothy sputum * Rapid, irregular heartbeat * Anxiety and restlessness * Cold, clammy skin * Wheezing or gasping for breath
What is the second most common cause of pulmonary hypertension?
Pulmonary Hypertension Associated with Lung Disease
What are some conditions associated with pulmonary hypertension in lung disease?
- Chronic obstructive pulmonary disease (COPD) * Interstitial lung disease * Sleep-related respiratory disorders
What percentage of COPD patients have mPAP >20 mmHg?
90%
What is the challenge with patients having primary lung disease and severe pulmonary hypertension?
They have poor clinical outcomes
What does venous thromboembolism (VTE) encompass?
Deep-venous thrombosis (DVT) and pulmonary embolism (PE)
VTE can lead to cardiovascular death, chronic disability, and emotional distress.
Where do venous thrombi typically originate?
Deep veins of the lower extremities, but also the upper extremities, right side of the heart, and pelvic veins
This is crucial for understanding the potential sources of thrombi.
What are the three components of Virchow’s triad related to the pathogenesis of thrombi?
- Stasis of blood
- Alterations in the blood coagulation system (hypercoagulability)
- Abnormalities of the vessel wall (intimal injury)
These factors contribute to the development of venous thromboembolism.
What is the most common autosomal dominant genetic mutation associated with hypercoagulability?
Factor V Leiden
This mutation causes resistance to activated protein C, an important anticoagulant.
What is antiphospholipid antibody syndrome?
An acquired thrombophilic disorder that predisposes to both venous and arterial thrombosis
It is not a genetic condition.
List three clinical risk factors for venous thromboembolism.
- Cancer
- Obesity
- Cigarette smoking
Other factors include systemic arterial hypertension, COPD, chronic kidney disease, and long-haul air travel.
What is the definition of pulmonary embolism?
Thrombi form in large veins and travel to the lungs where they become lodged in and occlude the pulmonary circulation
This condition is associated with significant morbidity and mortality.
What are the types of pulmonary emboli?
- Venous thrombi
- Nonthrombotic emboli: fat, air, and amniotic fluid
Understanding these types is essential for diagnosis and treatment.
True or False: Patients who suffer PE are more than twice as likely to have a future myocardial infarction or stroke.
True
This highlights the interconnected risks of thromboembolic events.
What characterizes a massive (high-risk) pulmonary embolism?
Systemic arterial hypotension and extensive thrombosis affecting at least half of the pulmonary vasculature
Symptoms may include dyspnea, syncope, hypotension, and cyanosis.
What is chronic thromboembolic pulmonary hypertension (CTEPH)?
Development of pulmonary hypertension after chronic thromboembolic obstruction of the pulmonary arteries
The incidence following a single PE event is between 3 and 7%.
What is cor pulmonale?
Right ventricular failure due to excessively high pulmonary artery pressures
It can be caused by pulmonary emboli, pulmonary vascular disease, or parenchymal disease.
What are the characteristics of vasculitis?
Inflammation of and damage to blood vessels, often leading to ischemia of the tissues supplied by the affected vessel
The clinical manifestations vary based on the size, type, and location of the involved vasculature.
What is the hallmark of sarcoidosis pathology?
Noncaseating granulomatous inflammation
This condition can affect any organ but most commonly targets the lungs and intrathoracic lymph nodes.
Fill in the blank: The finding of granulomas in sarcoidosis is not _______.
specific
Differential diagnoses include mycobacterial and fungal infections, malignancy, and environmental agents.
What are the stages of sarcoidosis based on radiographic findings?
- Stage 0: No pulmonary sarcoidosis
- Stage 1: Granulomas in lymph nodes only
- Stage 2: Granulomas in lymph nodes and lungs
- Stage 3: Granulomas in lungs only
- Stage 4: Pulmonary fibrosis
Each stage has distinct clinical implications.
What are common pulmonary function test results in sarcoidosis?
- Restrictive impairment with reduction in lung volumes
- Reduction in diffusing capacity
- Obstructive impairment in advanced disease
Resting hypoxemia and exercise O2 desaturation are also typical.
What are the complications of asbestos exposure?
- Nonmalignant pleural manifestations
- Asbestosis
- Malignant mesothelioma
- Lung cancer
Asbestos exposure is linked to various serious health conditions.
What happens during initial macrophage alveolitis in asbestos exposure?
Most fibers are cleared, leaving the lungs unscarred
If clearance is incomplete, fibrosis can ensue.
What are the malignant pleural manifestations related to asbestos exposure?
Malignant mesothelioma and lung cancer
Asbestos exposure is linked to serious lung diseases.
What is asbestosis?
Interstitial pneumonitis and fibrosis resembling other forms of diffuse interstitial fibrosis
Early lesions show discrete areas of fibrosis in respiratory bronchioles.
What characterizes the initial response to asbestos exposure?
Initial macrophage alveolitis, with most fibers cleared, leaving lungs unscarred
Incomplete clearance can lead to fibrosis.
What are the signs and symptoms of asbestosis?
Dyspnea, bibasilar rales, restrictive ventilatory impairment
Exposure duration and intensity should be assessed.
What is silicosis?
An occupational pulmonary hazard caused by free silica (SiO2)
It is characterized by acute alveolitis and ground-glass appearance.
What is chronic silicosis?
Characterized by small rounded opacities in the upper lobes after 15–20 years of exposure
Usually without associated impairment of lung function.
What are the complications associated with progressive massive silicosis?
Obstructive and restrictive ventilatory impairment, respiratory failure
It can also be associated with autoimmune disorders.
What is Coal Workers’ Pneumoconiosis (CWP)?
A disease due to occupational exposure to coal dust
It has significant social, economic, and medical implications.
What are the radiographic findings in simple CWP?
Simple radiographically identified CWP seen in ~10% of coal miners
Not associated with pulmonary impairment.
What is Caplan syndrome?
A combination of coal/silica exposure and rheumatoid arthritis
It is associated with complicated Coal Workers’ Pneumoconiosis.
What is a coal macule?
A focal collection of coal dust in macrophages around respiratory bronchioles
It is a fundamental histopathologic finding in CWP.
What are the possible physiological defects in CWP?
Obstructive, restrictive, or mixed defects
The predominant abnormality depends on the individual’s lung pathology.
What is Beryllium Disease?
A disease associated with industrial exposure to beryllium, with a long latency period
It can manifest as acute pneumonitis or chronic granulomatous disease.
What is the primary classification method for bacteria?
By staining: Gram-positive vs. Gram-negative
Gram-positive bacteria stain blue, while gram-negative bacteria stain red.
What distinguishes Gram-positive from Gram-negative bacteria?
Gram-positive bacteria have a thick peptidoglycan cell wall
This structural difference affects their staining and susceptibility to antibiotics.
What are the two main types of bacteria based on oxygen requirement?
Aerobic and anaerobic
Aerobes need oxygen for growth, while anaerobes have difficulties growing in its presence.
What are the morphological classifications of bacteria?
Spherical (cocci), cylindric (bacilli), spiral (spirochetes)
These shapes help in identifying bacterial species.
What are two important Gram-positive cocci pathogens?
Staphylococcus aureus and Streptococcus pyogenes
They are differentiated by their morphology and biochemical properties.
How do staphylococci appear microscopically?
In grapelike clusters
This is different from streptococci, which appear in chains.
What biochemical property is used to differentiate staphylococci from streptococci?
Staphylococci produce catalase, while streptococci do not
This difference is important for laboratory identification.
What are the two main criteria that differentiate staphylococci from streptococci?
Microscopic appearance and biochemical properties.
Staphylococci appear in grapelike clusters, while streptococci are arranged in chains. Staphylococci produce catalase; streptococci do not.
What is the shape and arrangement of Staphylococcus aureus?
Spherical gram-positive cocci arranged in irregular grapelike clusters.
Staphylococcus aureus produces catalase, which is important for its virulence.
List the three species of Staphylococcus.
- S. aureus
- S. epidermidis
- S. saprophyticus
What distinguishes Staphylococcus aureus from other species?
Coagulase production.
Coagulase is an enzyme that causes the clotting of blood.
Where is the main site of colonization for Staphylococcus aureus in humans?
The nose.
Approximately 30% of people are colonized at any one time.
What are the three exotoxins produced by Staphylococcus aureus?
- Enterotoxin
- Toxic Shock Syndrome Toxin
- Exfoliatin
What type of diseases does Staphylococcus aureus cause?
Pyogenic (pus-producing) diseases and diseases caused by toxins.
Examples include abscesses, folliculitis, and toxic shock syndrome.
What are the important properties of streptococci?
Spherical gram-positive cocci arranged in chains or pairs, and all are catalase negative.
What are the groups of streptococci based on antigenic differences?
Groups A–U (Lancefield groups).
What is the most important human pathogen among Group A streptococci?
Streptococcus pyogenes.
What is the hemolytic pattern of α-hemolytic streptococci?
A green zone around colonies due to incomplete lysis of red blood cells.
What does β-hemolytic streptococci produce that causes complete lysis of red blood cells?
Enzymes called hemolysins, specifically streptolysin O and streptolysin S.
What are the three types of diseases caused by Streptococcus pyogenes?
- Pyogenic diseases
- Toxigenic diseases
- Immunologic diseases
What is the leading cause of neonatal sepsis and meningitis?
Streptococcus agalactiae (Group B Streptococcus).
What is the common cause of community-acquired pneumonia?
Streptococcus pneumoniae.
What enhances the ability of S. pneumoniae to colonize the mucosa of the upper respiratory tract?
IgA protease.
What are the main risk factors for pneumonia?
- Defects in normal defense mechanisms
- Large infectious inoculum
- Virulent pathogens
What are the most common viral causes of community-acquired pneumonia?
- Coronaviruses (SARS-CoV-2, MERS)
- Influenza virus
- Respiratory syncytial virus
- Adenovirus
- Parainfluenza virus
What is a common diagnostic test for community-acquired pneumonia?
Sputum Gram stain and culture.
What is the typical clinical presentation for community-acquired pneumonia?
- Fever (>38°C)
- Leukopenia or leukocytosis
- Altered mental status in adults ≥70 years
- New onset of purulent sputum
- New-onset or worsening cough, dyspnea, or tachypnea
What is the difference between typical and atypical pneumonia?
Typical pneumonia is caused by organisms like S. pneumoniae, while atypical pneumonia is caused by organisms such as Mycoplasma, Chlamydia, and Legionella.
What is leukopenia?
Leukopenia is defined as a white blood cell count of <4000 WBC/mm3.
What is leukocytosis?
Leukocytosis is defined as a white blood cell count of ≥12,000 WBC/mm3.
What altered mental status criteria is significant in adults ≥70 years of age?
Altered mental status without an alternative etiology.
What are the symptoms indicating new onset of pneumonia?
New onset of purulent sputum, change in sputum character, or increased secretions/suction requirements.
What respiratory symptoms indicate pneumonia?
New-onset or worsening cough, dyspnea, or tachypnea.
What are rales?
Rales are abnormal lung sounds indicative of fluid in the alveoli.
What characterizes typical CAP pneumonia?
The X-Ray corresponds with clinical findings on physical examination.
What is lobar pneumonia?
Lobar pneumonia is acute exudative inflammation of the entire lobe with uniform consolidation.
Which pathogen is the majority cause of lobar pneumonia?
Streptococcus pneumoniae.
What is bronchopneumonia?
Bronchopneumonia is a type of pneumonia that inflames the alveoli with incomplete consolidation.
What are the updated recommendations for the pneumococcal vaccine?
Either PCV20 alone or sequential administration of PCV15 and PPSV23.
Who should receive the pneumococcal vaccine?
Adults aged 65 years or older and those with comorbidities.
What is atypical pneumonia?
Atypical pneumonia is characterized by X-Ray findings not corresponding with clinical examination.
What is the transmission method for Mycoplasma pneumoniae?
Transmitted by respiratory droplets.
What percentage of pneumonia cases are due to Mycoplasma pneumoniae?
~20% of pneumonia cases.
What age group has the highest incidence of Mycoplasma pneumoniae infection?
Older children and young adults (ages 5-20 years).
What is Chlamydia pneumoniae known to cause?
Pharyngitis, bronchitis, and atypical pneumonia.
What is the significance of C. pneumoniae antibodies in adults?
About 50% of adults in the U.S. have antibodies to C. pneumoniae.
How does Legionella enter the respiratory tract?
By aspiration of contaminated water or inhalation of aerosol.
What is Legionnaires disease?
An atypical, acute lobar pneumonia with multisystem symptoms.
What differentiates community-acquired pneumonia from nosocomial pneumonia?
Different infectious causes, antibiotic susceptibility patterns, and patient health status.
What types of pneumonia are included in nosocomial pneumonia?
Hospital-acquired pneumonia (HAP) and ventilator-acquired pneumonia (VAP).
What are common risk factors for HAP?
- Instrumentation of the upper airway
- Treatment with broad-spectrum antibiotics
- Advanced age
- Impaired cellular defense mechanisms
What are the microbiological differences between CAP and HAP?
HAP microbiology differs from CAP and includes resistant organisms.
What is the most common etiology of early HAP?
Enteric gram-negative bacilli (E. coli, K. pneumoniae, etc.).
What is a lung abscess?
A necrotizing lung infection characterized by a pus-filled cavitary lesion.
What is the most common cause of lung abscess?
Aspiration of oral secretions.
What are common symptoms of lung abscess?
- Productive cough
- Fever
- Weight loss
What is the primary treatment for lung abscess?
Combination beta-lactam/beta-lactamase inhibitor or a carbapenem.
What is the historical significance of tuberculosis?
One of the oldest diseases known to affect humans.
What is the global impact of tuberculosis?
The top cause of infectious death worldwide excluding COVID-19.
What family does Mycobacterium tuberculosis belong to?
Family Mycobacteriaceae.
What is zoonotic tuberculosis?
M. bovis transmitted by unpasteurized milk.
What is the shape and size of M. tuberculosis?
Rod-shaped, non-spore-forming, thin aerobic bacterium measuring 0.5 μm by 3 μm
How are M. tuberculosis bacilli classified?
As acid-fast bacilli due to their inability to be decolorized by acid alcohol after Gram-staining
What is the primary mode of transmission for M. tuberculosis?
Through droplet nuclei from infectious pulmonary TB, aerosolized by coughing, sneezing, or speaking
What size droplets containing M. tuberculosis can remain suspended in the air?
Droplets smaller than 5–10 μm in diameter
What is the estimated number of infectious nuclei per cough from an infected individual?
Up to 3000 infectious nuclei
List two types of transmission risk factors for M. tuberculosis.
- Exogenous
- Endogenous
What are exogenous risk factors for M. tuberculosis transmission?
- Crowding in poorly ventilated rooms
- Sputum smear–positive cases
What are some endogenous risk factors for M. tuberculosis?
- Degree of immune competence
- HIV-infected patients
- Cancer treatment
- Immunosuppressive drugs
What is primary TB?
Clinical illness directly following infection, common among children and immunocompromised persons
What is miliary tuberculosis?
A severe and disseminated form of TB that is generally not associated with high-level transmissibility
What characterizes post-primary TB in adults?
Reactivation or reinfection of TB later in life; more often infectious than primary disease
What percentage of infected persons will develop active TB in their lifetime?
Up to 10%
What are common clinical symptoms of TB?
- Fatigue
- Nocturnal sweating
- Increased temperature
- Weight loss
- Cough with expectoration
- Hemoptysis
- Pleural pain (rarely)
- Dyspnea (rarely)
What is the purpose of the Tuberculin Test?
To detect TB infection through intradermal injection of tuberculin (PPD-RT)
What indicates active infection on a Tuberculin Test?
More than 15 mm induration
What is atelectasis?
A medical condition characterized by the collapse or incomplete expansion of a part or all of the lung
Name the major types of atelectasis.
- Resorption atelectasis
- Compression atelectasis
- Contraction atelectasis
What causes resorption atelectasis?
Blocking of an airway leading to a portion of the lung, preventing air from reaching the alveoli
List some major causes of resorption atelectasis.
- Aspiration of a foreign body
- Tumor or other growth
- Mucous plug
What is compression atelectasis?
Occurs when there is external pressure on the lung, preventing it from expanding fully
What is the normal function of the pleura?
- Protection
- Lubrication
- Support
What are the two layers of the pleura?
- Visceral Pleura
- Parietal Pleura
What is pleural effusion?
An abnormal collection of fluid in the pleural space
Differentiate between transudative and exudative pleural effusions.
- Transudate: Protein- and cell-poor fluid
- Exudate: Rich in protein and often cells
What are some causes of transudative pleural effusions?
- Congestive heart failure
- Cirrhosis
- Nephrotic syndrome
- Constrictive pericarditis
What is parapneumonic effusion?
Accumulation of fluid in the pleural space as a complication of pneumonia
What are the three main types of infectious pleural effusions?
- Uncomplicated
- Complicated
- Empyema
What symptoms are caused by pleural effusion?
- Dyspnea
- Chest pain
True or False: Late treatment of serious infectious effusions can threaten a patient’s life.
True
Fill in the blank: The ________ is a specialized type of epithelial tissue that lines body cavities.
[mesothelium]
What does the mesothelium consist of?
A single layer of flattened to cuboidal cells known as mesothelial cells
What is the normal intrapleural pressure?
Around -10 cm water at the lung bases
What is the mnemonic used in medicine regarding parapneumonic effusions?
The phrase emphasizes the urgency of diagnosing and treating parapneumonic effusions promptly before sunset.
Timely intervention is crucial to prevent complications.
What is the typical treatment for parapneumonic effusions that progress to empyema?
Draining the fluid and sometimes using clot-busting drugs and DNA-ase enzymes.
These treatments improve drainage and reduce complications.
What are transudates and exudates in the context of pleural effusions?
Transudates are typically bilateral, while exudates can be uni- or bilateral.
Exudates require further investigation to rule out cancer.
What is the initial study for diagnosing pleural effusions?
Chest radiograph is a decent initial study, both upright and decubitus.
Ultrasound and CT are more effective in detecting effusions.
What are the two meanings of ‘influenza’?
- Syndrome: systemic symptoms of fever, malaise, myalgia, and respiratory symptoms
- Microbe: influenza virus that infects the respiratory tract.
The systemic symptoms typically accompany the syndrome.
What are the two most clinically important types of influenza viruses?
Influenza A and Influenza B.
Both are orthomyxoviruses and negative-sense single-stranded RNA viruses.
What are the major proteins relevant to influenza?
- Neuraminidase
- Viral hemagglutinin
- RNA-dependent RNA polymerase proteins.
These proteins play crucial roles in viral entry and replication.
What is antigenic shift in influenza viruses?
A sudden and major change in the antigenic properties due to the exchange of genetic material between different influenza viruses.
This can lead to the emergence of new subtypes capable of causing pandemics.
What is antigenic drift in influenza viruses?
Gradual and incremental changes in the antigenic properties due to mutations in the viral genome.
This leads to seasonal influenza epidemics as the virus evolves to evade immunity.
What is the life cycle of Influenza A or B characterized by?
Binding due to hemagglutinin and budding due to neuraminidase.
These processes are essential for viral entry and spread.
What are the common clinical features of influenza?
- Cough
- Sore throat
- Rhinorrhea
- Systemic symptoms like fatigue and myalgias.
Symptoms typically develop over hours with a brief incubation period.
What are potential complications of influenza?
- Bacterial superinfection
- Severe pneumonia
- Myocarditis
- Guillain-Barre syndrome.
Complications can lead to significant morbidity and mortality.
How is influenza diagnosed?
Diagnosis is usually clinical, confirmed by NAAT tests (nasopharyngeal swab).
Serology is not typically used for diagnosis.
What factors influence the severity of influenza epidemics?
- Antibody effectiveness
- Ability to transmit from human to human
- Other virulence factors.
These factors determine the clinical impact of influenza outbreaks.
What is the role of the immune response in influenza infection?
Activates innate and adaptive immune mechanisms to target and eliminate virus-infected cells.
Excessive immune response can lead to severe symptoms and complications.
What is the typical treatment for severe influenza?
Neuraminidase inhibitors are used if given within 48 hours of onset.
Vaccinations have a modest effect on reducing symptoms and hospitalizations.
What is the general microbiology of COVID-19?
Caused by SARS-CoV-2, a betacoronavirus, with a single linear RNA segment of nearly 30,000 nucleotides.
It encodes four structural proteins: S, E, M, and N.
What is the primary mode of transmission for COVID-19?
Droplet transmission, including larger droplets and smaller aerosols.
Contact with contaminated surfaces can also lead to infection.
What are the systemic symptoms associated with influenza?
- Fatigue
- Myalgias
- Shaking chills
- Headache.
These symptoms often accompany respiratory symptoms.
What appearance does SARS-CoV-2 give?
Crown of thorns or a solar corona
Name the surface proteins associated with SARS-CoV-2.
- Hemagglutinin-acetylesterase glycoprotein
- Membrane glycoprotein
- Small envelope glycoprotein
What are the modes of transmission for SARS-CoV-2?
- Droplet transmission
- Contact from colonized surfaces
What types of droplets are involved in droplet transmission?
- Larger droplets that fall to the ground quickly
- Smaller droplets (aerosols) that remain airborne longer
What initial cells are targeted for viral colonization by SARS-CoV-2?
Nasopharyngeal/oropharyngeal cells
Which cells can be invaded by SARS-CoV-2 after initial colonization?
- Bronchial epithelium
- Alveolar epithelial cells
- Vascular endothelial cells
- Alveolar macrophages
What types of vascular endothelial cells can SARS-CoV-2 invade?
- Heart endothelial cells
- Kidney endothelial cells
Which other cell types express ACE-2?
- Enterocytes
- Cholangiocytes
- Myocardial cells
- Kidney cells
- Bladder urothelial cells
Why is COVID-19 so transmissible?
It replicates in the upper airways
In which stages of infection does SARS-CoV-2 replicate?
- Symptomatic stages
- Pre-symptomatic stages
How does the transmissibility of SARS-CoV-2 compare to SARS-CoV-1 and MERS?
SARS-CoV-2 is more transmissible; SARS-CoV-1 and MERS have higher death rates
What is the R0 rate for SARS-CoV-2?
Between 5 and 6
What is the R0 rate for influenza?
Between 1 and 2
Does enteric replication impact the transmissibility of SARS-CoV-2?
No one is sure; likely not
What effect does enteric replication have during symptomatic phases?
Exacerbates inflammation
What is the function of the spike protein’s receptor binding domain?
Binds to the ACE2 enzyme on cells
What allows for viral entry into host cells?
Cleavage of the spike protein by TMPRSS2
What forms after the cleavage of the spike protein?
Endosome
What happens after the viral genome is released in the cytoplasm?
Translation in a polyprotein followed by cleavage
What are some functions of the proteins produced after viral genome translation?
- Continued replication (RNA-dependent RNA polymerase)
- Viral particle assembly
- Inhibition of type I interferons
How does SARS-CoV-2’s mutation rate compare to influenza?
Relatively low rate of mutation due to exonuclease activity
What is a cytokine storm?
A hyper-inflammatory response triggered by highly virulent viruses such as H5N1, H1N1, and COVID-19
It leads to acute respiratory distress syndrome (ARDS) in infected patients.
Which cytokines are primarily involved in a cytokine storm?
Interferon-γ, TNF-α, IL-1, IL-6
These proinflammatory cytokines stimulate multiple organ systems.
What is the role of TMPRSS2 in early lung inflammation?
Promotes viral uptake by cleaving ACE2 and activating the SARS-CoV-2 S-protein
This process facilitates the infection of bronchial epithelial cells and alveolar pneumocytes.
What occurs during late lung inflammation in COVID-19?
Release of kinins activates kinin receptors, leading to vascular smooth muscle relaxation and increased permeability
This is controlled by the ACE2 receptor.
What are the symptoms associated with mild to moderate COVID-19?
Fever, cough, shortness of breath, fatigue, muscle aches, headache, loss of taste or smell, sore throat, congestion, nausea, diarrhea
Approximately 80% of symptomatic individuals experience these symptoms.
What percentage of COVID-19 patients remain asymptomatic?
Approximately 30%
This indicates a significant portion of individuals do not exhibit symptoms despite being infected.
What are the severe symptoms of COVID-19?
Dyspnea, cyanosis, chest pain, confusion, inability to wake
Severe symptoms can lead to complications like ARDS and multi-organ failure.
What is the estimated mortality rate of COVID-19?
Just over 2%
This estimate is based on the global death toll, which is approximately 7 million.
What major factors increase the risk of severe COVID-19 complications?
- Advanced age
- Male sex
- Racial and ethnic minorities
- Chronic conditions (cardiovascular disease, diabetes, etc.)
- Immunocompromised status
Over 80% of deaths occur in individuals over age 65.
What do the kidneys do?
Produce urine and convey it via ureters to the urinary bladder
They also interact with suprarenal glands, which are part of the endocrine system.
Where do the renal arteries arise?
At the level of the IV disc between the L1 and L2 vertebrae
The right renal artery passes posterior to the IVC.
What structures enter and exit the renal sinus through the renal hilum?
Vessels, nerves, and structures that drain urine from the kidney
The hilum is the entrance to the renal sinus.
What is the role of the renal nerve plexus?
Supplies sympathetic and parasympathetic fibers to the kidneys
It is involved in the autonomic regulation of kidney function.
What are umbrella cells?
Specialized epithelial cells in the urinary bladder that maintain wall integrity
They are resistant to urine and facilitate bladder expansion.
What is the function of the internal urethral sphincter?
Controls involuntary urine flow from the bladder to the urethra
In males, it also prevents the flow of semen into the bladder during ejaculation.
What is micturition?
The process of bladder emptying, involving complex neural circuitry
It allows for voluntary control based on perceived bladder fullness.
Fill in the blank: The _______ is released from tonic inhibitory control to initiate the voiding process.
pontine micturition center
What are the two types of nerves that supply the bladder?
- Sympathetic fibers
- Parasympathetic fibers
They regulate bladder function during filling and voiding phases.
What is a unique feature of COVID-19 related hypoxemia?
Significant hypoxemia (< 90% oxygen saturation) with limited dyspnea
This unusual symptom warrants further investigation into its mechanisms.
What are umbrella cells?
Superficial specialized epithelial cells found in the lining of the urinary tract, particularly in the urinary bladder.
What is the role of umbrella cells in the bladder?
Maintain the integrity and impermeability of the bladder wall.
How do umbrella cells adapt their apical membrane?
They have numerous densely packed, rigid, hexagonally arranged Uroplakin plaques.
What is the function of tight junctions in umbrella cells?
Create a barrier that regulates the movement of ions, water, and solutes across the epithelium.
What allows umbrella cells to accommodate changes in bladder volume?
The apical surface can expand and contract significantly.
What provides structural support to umbrella cells?
Cytokeratin filaments and actin bundles.
What specialized transport mechanisms do umbrella cells possess?
They express aquaporin water channels to facilitate the rapid reabsorption of water.
What is uroplakin turnover?
The continuous synthesis and turnover of uroplakins to maintain the apical membrane integrity.
What does the term ‘vesicoureteric’ refer to?
The junction between the urinary bladder and the ureter.
What is vesicoureteral reflux (VUR)?
A condition where urine flows backward from the bladder into one or both ureters.
How is vesicoureteral reflux classified?
Into different grades from I (mildest) to V (most severe).
What are the typical symptoms of uncomplicated cystitis?
Dysuria, urinary frequency, urgency.
What distinguishes complicated cystitis from uncomplicated cystitis?
Unilateral back or flank pain and fever suggest involvement of the upper urinary tract.
What is pyelonephritis?
A kidney infection that can present with fever, flank pain, and other symptoms.
What is the main feature distinguishing cystitis from pyelonephritis?
Fever.
What is urosepsis?
A systemic inflammatory response due to bacteria from the urinary tract entering the bloodstream.
What is the predominant microorganism in normal vaginal microbiota?
Lactobacillus species.
What role do Lactobacillus species play in vaginal health?
They create an acidic environment and produce antimicrobials to inhibit harmful bacteria.
What increases the risk factors for urinary tract infections?
- Obstruction
- Short urethra length
- Bladder catheterization.
What is the most frequent pathogen causing urinary tract infections?
E. coli.
What are P fimbriae?
Hair-like protein structures that help E. coli bind to specific receptors on uroepithelial cells.
True or False: Asymptomatic bacteriuria always requires treatment.
False.
Fill in the blank: The typical symptoms of _______ cystitis include dysuria, urinary frequency, and urgency.
uncomplicated
What amino acids are required for optimal growth of Proteus?
Guanine, arginine, and glutamine
These amino acids are essential for the bacterial synthesis and growth of Proteus
What role do ureases produced by Proteus mirabilis play in pyelonephritis?
They generate ammonium, raising urine pH above 7
This alkaline urine enhances bacterial growth and increases the likelihood of renal stones.
How does alkaline urine affect bacterial growth?
Enhances bacterial growth and increases likelihood of renal stones
Alkaline conditions promote the survival and proliferation of certain bacteria.
What immunological factor does Proteus produce?
Immunoglobulin A (IgA) protease
This factor helps the bacteria evade immune responses.
What is the function of flagella in Proteus?
Allows bacteria to migrate up the urethra and adhere to epithelial cells
The expression of flagella is regulated by operons responding to external conditions.
How do endotoxins contribute to pyelonephritis?
Decrease ureteral peristalsis, slowing urine flow
This enhances the ability of gram-negative bacteria to ascend into the kidneys.
What is a key characteristic of Klebsiella bacteria in healthcare settings?
Adhere to and colonize mucosal surfaces of the bladder or kidney tissues
This adherence is facilitated by fimbriae and adhesins.
What mechanisms do Klebsiella use to evade the immune system?
Invade bladder epithelial cells
This allows them to evade detection and persist within the urinary tract.
What is the significance of biofilm formation in Klebsiella infections?
Provides protection against antibiotics and host immune responses
Biofilms make eradication of infections more challenging.
List some virulence factors produced by Klebsiella.
- Capsule polysaccharides
- Lipopolysaccharides (LPS)
- Siderophores
- Toxins
These factors aid in evading host defenses and causing tissue damage.
What is a common association with enterococcal UTIs?
Indwelling catheterization, instrumentation, or anatomic abnormalities
These factors increase the risk of enterococcal infections.
What are the clinical manifestations of interstitial cystitis?
Discomfort and/or pain perceived to be related to the bladder, urinary frequency, and urgency
This severely impacts quality of life and social interactions.
What are some proposed etiologies of interstitial cystitis?
- Infection and the urinary microbiota
- Autoimmunity
- Inflammation
- Urothelial dysfunction
These factors may contribute to the pathophysiology of the condition.
What is the primary function of the urothelium?
Provide a robust barrier layer
This is achieved through glycosaminoglycans (GAGs) and tight junctions among urothelial cells.
What is the clinical relevance of Hunner lesions in interstitial cystitis?
Discrete inflammatory lesions associated with a well-characterized inflammatory profile
They are identifiable via cystoscopy and are indicative of bladder inflammation.
What is the economic impact of interstitial cystitis?
Similar to fibromyalgia, low back pain, rheumatoid arthritis, and peripheral neuropathy
Associated disability can significantly affect quality of life.
What is the most common site of urinary tract tumors?
Urinary bladder
Bladder cancer is the most prevalent urologic malignancy.
What are the most common types of bladder tumors?
- Urothelial malignant neoplasms
- Squamous cell cancers
- Adenocarcinomas
- Neuroendocrine malignancies
- Sarcomas
Urothelial tumors account for 90% of bladder cancers.
What factors increase the risk of bladder cancer?
- Cigarette smoking
- Industrial exposure to azo dyes
- Infection with S. haematobium
- Certain drugs and radiation therapy
These factors contribute to a significant percentage of new bladder cancer cases.
What is a urothelial papilloma?
Benign tumors usually discovered incidentally during cystoscopy
They represent less than 1% of bladder tumors.
What characterizes urothelial carcinoma in situ?
Full-thickness lesions confined to the bladder mucosa
Associated with a risk of subsequent invasive carcinoma.
What is the clinical presentation of urothelial carcinoma?
Sudden hematuria and less often dysuria
At presentation, 85% of tumors are confined to the bladder.
What diagnostic tools are used for bladder cancer?
- Urinalysis
- Imaging studies (Ultrasound, CT, MRI)
These are crucial for evaluating bladder masses and staging.
What percentage of tumors are confined to the urinary bladder?
85%
15% show regional or distant metastases.
What system is used for staging bladder cancers?
Tumor node metastasis (TNM) system
What are the common sites of metastases for bladder cancer?
- Regional lymph nodes
- Periaortic lymph nodes
- Liver
- Lung
- Bone
What does urinalysis commonly detect in bladder cancer?
- Hematuria
- Pyuria
What imaging studies are useful for bladder cancer evaluation?
- Ultrasound
- CT
- MRI
What is the sensitivity of urine cytology for detecting higher grade and stage cancers?
80–90%
What procedures are used for diagnosis and staging of bladder cancer?
- Cystourethroscopy
- Tumor biopsy
- Random bladder biopsies
- Transurethral prostate biopsies
What is TURBT?
Transurethral resection of bladder tumor
What are the three stages of the nephric system?
- Pronephros
- Mesonephros
- Metanephros
What is the main function of the pronephros?
Temporary filtration system
When does the pronephros disappear?
By the 4th week
What structures develop from the mesonephros?
- Bowman’s capsule
- Glomerulus
What is the significance of the metanephros?
Primitive proper kidney
At what level does the metanephros arise?
Opposite the 28th somite (L4)
What are the anatomical features of the kidneys?
- Bean-shaped organs
- Located under the rib cage
- Close to the posterior abdominal wall
What is the flow path of urine in the kidneys?
- Pyramids
- Papilla
- Minor calyx
- Major calyx
- Renal pelvis
- Ureter
What is the functional unit of the kidney?
Nephron
What are the two arterioles associated with the renal corpuscle?
- Afferent arteriole
- Efferent arteriole
What is the function of glomerular mesangial cells?
- Remove trapped material
- Provide physical support
- Release cytokines
- Maintain filtration rate
What is the main role of podocytes?
Support structures with a sieving role in filtration
What does the proximal convoluted tubule primarily reabsorb?
- Water
- Glucose
- Amino acids
- Ions
What is the purpose of the loop of Henle?
Establish concentration gradient in the medulla
What specialized cells mark the end of the thick ascending limb?
Macula densa
What type of cells are found in the distal convoluted tubule?
- Principal cells
- Intercalated cells
What is the function of the collecting duct?
Water reabsorption and ion balance
What are the three constriction sites of the ureters?
- Renal pelvis
- Pelvic brim
- Entrance to the bladder
Where does the ureter enter the bladder?
Posterolaterally via the trigone
What is the detrusor muscle responsible for?
Contraction causes urination
What type of muscle is the internal urethral sphincter?
Smooth muscle
What nerve innervates the external urethral sphincter?
Pudendal nerve (S2–S4)
What are the vascular supplies to the urinary bladder?
- Superior vesical arteries
- Inferior vesical arteries
- Vaginal arteries (in females)
What is the micturition reflex?
Process initiated by bladder distension leading to urination
What are the three parts of the male urethra?
- Prostatic
- Membranous
- Penile
What is the histological feature of the mucosa of the calyx?
Dense connective tissue and adipose tissue
What do interlobular arteries give off in the cortex?
Afferent arterioles
Afferent arterioles bring blood to the glomerular capillaries.
What is the composition of the parietal layer of a glomerular capsule?
Simple squamous epithelium supported by a basal lamina.
What type of epithelium is found at the tubular pole of the glomerular capsule?
Simple cuboidal epithelium.
What are podocytes?
Unusual stellate epithelial cells in the visceral layer of the glomerular capsule.
What do primary processes of podocytes do?
Extend and curve around a length of glomerular capillary.
What are pedicels?
Parallel, interdigitating secondary processes from podocytes.
Where are filtration slit pores located?
Between the pedicels.
What bridges the slit pores in the glomerular filtration barrier?
Zipper-like slit diaphragms.
What is the role of the glomerular basement membrane?
Separates blood from the capsular space.
What type of epithelium lines the proximal convoluted tubule (PCT)?
Simple cuboidal epithelium.
What feature of proximal tubule cells facilitates reabsorption?
Long microvilli forming a brush border.
What characterizes the thin descending and ascending limbs of the loop of Henle?
Composed of simple squamous epithelia.
What type of cells are found in the distal convoluted tubule (DCT)?
Simple cuboidal cells.
How do the cells of DCT differ from those of PCT?
DCT cells are smaller and lack a brush border.
What is the macula densa?
Columnar and closely packed cells at the vascular pole.
What is the function of juxtaglomerular (JG) cells?
Secrete renin.
What type of cells are principal cells in the collecting ducts?
Pale-staining cells with few organelles.
What is the primary function of principal cells?
Ion transport.
What type of epithelium lines the ureters?
Urothelium (transitional epithelium).
What are the three layers of urothelium?
- Basal cells
- Intermediate region
- Umbrella cells.
What type of epithelium lines the prostatic urethra in males?
Urothelium.
What epithelium lines the membranous urethra in males?
Stratified columnar and pseudostratified columnar epithelium.
What type of epithelium does the female urethra transition to?
Nonkeratinized stratified squamous epithelium.
What is the functional unit of the kidney?
Nephron.
What are the two parts of the nephron?
- Glomerulus
- Bowman’s capsule.
What are the two types of nephrons?
- Cortical nephrons
- Juxtamedullary nephrons.
What is the primary function of the glomerulus and Bowman’s capsule?
Site where blood is filtered through a specialized membrane.
What is the primary function of the proximal convoluted tubule?
Reabsorb the majority of solutes and water.
What do loops of Henle contribute to?
Concentration of urine.
What is renal clearance?
Volume of plasma from which a substance is completely removed by the kidneys per unit of time.
What factors determine filtration in the kidneys?
Starling forces and permeability of the filtration membrane.
What are the three ways the kidneys handle substances?
- Filtration
- Secretion
- Reabsorption.
What is glomerular filtrate?
Initial filtrate containing substances that will become urine.
What is the renal blood flow in terms of cardiac output?
1 L of blood/min (about 20% of the cardiac output)
Renal blood flow is much higher than the metabolic demand of the kidney.
What is the renal plasma flow (RPF)?
600 ml/min available for filtration
This is the volume of plasma that is filtered at the glomerulus.
What is the glomerular filtration rate (GFR) for most people with good renal function?
120 ml/min
This is approximately 20% of the renal plasma flow.
What does eGFR stand for?
Estimated glomerular filtration rate
It estimates how well kidneys filter waste products from the blood.
What is the normal range for eGFR?
Above 90 mL/min/1.73m²
Values below this indicate decreased kidney function.
What are the components of the filtration barrier in the glomerulus?
- Fenestrations in glomerular capillaries
- Basement membrane
- Filtration slits between podocytes
These components are crucial for the filtration process.
What types of molecules can pass through the glomerular filtration barrier?
- Water
- Ions
- Glucose
- Amino acids
- Waste products
Larger molecules like proteins and blood cells are retained.
What is the role of charged ions in the glomerular filtration process?
They contribute to the selective permeability of the filtration barrier
The barrier is permeable to ions but relatively impermeable to larger charged molecules.
What is the equation for net filtration pressure (NFP) across the glomerulus?
NFP = Kf · (PGC – PBC – πGC)
This equation takes into account the pressures involved in filtration.
How does constricting the afferent arteriole affect GFR?
Decreases GFR
It impacts the delivery of blood to the capillary.
What is autoregulation in the context of GFR?
The glomerulus maintains a relatively constant GFR despite changes in systemic blood pressure
It involves intrinsic mechanisms like myogenic response and tubuloglomerular feedback.
What happens during tubuloglomerular feedback when too much solute is delivered to the macula densa?
Less renin is secreted, leading to a drop in GFR
ATP or adenosine released by the macula densa plays a role in this feedback mechanism.
What is the effect of angiotensin II on GFR?
Increases GFR by constricting the efferent arteriole more than the afferent arteriole
This results in increased overall renal resistance.
What is azotemia?
Low filtration at the glomerulus, leading to a buildup of waste in the blood
It can be categorized into pre-renal, renal, and post-renal azotemia.
What substance can be used to measure GFR as it is only filtered and not secreted or reabsorbed?
Inulin
It must reach a steady state in the bloodstream for accurate measurement.
What is the significance of creatinine in measuring GFR?
It is filtered and has a small amount secreted, used to estimate GFR
Creatinine clearance requires blood and urine samples.
What is the major body fluid compartment distribution?
- 60% or greater of the body is water
- 2/3 intracellular (27 L)
- 1/3 extracellular
- Blood plasma is about 3 L (20% of ECF)
Understanding fluid compartments is important for kidney function.
What is hyponatremia?
A condition characterized by low sodium levels in the blood.
If a person has hyponatremia, have they reduced their secretion of sodium into the urine?
No, the kidney may be the problem.
What is the total body water percentage?
60% or greater.
How is body water distributed between intracellular and extracellular compartments?
2/3 intracellular (27 L) and 1/3 extracellular.
What is the volume of blood plasma?
About 3 L (20% of ECF).
What is the volume of interstitial fluid?
About 10-11 L (80% of ECF).
What happens when fluid or salt is added to the bloodstream?
It spreads freely between the ECF spaces but may not easily spread to the intracellular space.
What are the major cellular transport mechanisms involved in nephron function?
- Passive Diffusion
- Facilitated Diffusion
- Active Transport
- Secondary Active Transport (Symport and Antiport)
- Endocytosis and Exocytosis
Define passive diffusion.
Movement of molecules across the tubular epithelium down their concentration gradient without energy.
What is facilitated diffusion?
Movement of molecules across the cell membrane through specific carrier proteins or channels.
What is active transport?
Movement of molecules against their concentration gradient, requiring energy (ATP).
What is the role of the Na+/K+-ATPase pump?
It actively transports sodium ions out of tubular epithelial cells and potassium ions into the cell.
What does secondary active transport involve?
Coupled movement of two or more molecules across the cell membrane.
What is the difference between symport and antiport?
- Symport: molecules move in the same direction
- Antiport: molecules move in opposite directions.
What is endocytosis?
Process by which cells engulf extracellular substances by forming vesicles.
What is exocytosis?
Process where vesicles containing substances fuse with the cell membrane, releasing contents.
What are the approximate concentrations of Na+, K+, Cl-, and HCO3- in ICF and ECF?
Know approximate values for these ions.
What is insensible water loss?
Water loss from the skin that we are not aware of.
What are the two major routes of renal tubule transport?
- Transcellular route
- Paracellular route
What fraction of body weight is water?
About 60%.
What is the osmotic content of extracellular fluid primarily accounted for by?
- Sodium
- Chloride
What percentage of filtered sodium is reabsorbed in the proximal tubule?
About 65%.
What is the primary active transport mechanism for sodium reabsorption?
Na-K-ATPase pumps in the basolateral membrane.
What is the final urine sodium content?
Less than 1% of the total filtered sodium.
What is the role of chloride reabsorption in the kidneys?
Chloride is reabsorbed similarly to sodium, maintaining electroneutrality.
What is the primary mechanism for water reabsorption in the proximal tubule?
Water follows sodium reabsorption.
What is the function of aquaporins in renal cells?
Facilitate water reabsorption across cell membranes.
What occurs in the descending limb of Henle’s loop?
Water is reabsorbed.
What occurs in the ascending limb of Henle’s loop?
Sodium is reabsorbed.
What is the significance of the Na+/K+ ATPase in the nephron?
Establishes electrochemical gradients for reabsorption.
What substances are primarily reabsorbed by the proximal convoluted tubule (PCT)?
- Sodium
- Glucose
- Amino acids
- Bicarbonate
- Water
What is sodium-glucose co-transport?
Mechanism where sodium ions are transported into PCT cells along with glucose.
What happens to glucose after it enters the PCT cell?
Exits via facilitated diffusion into the bloodstream.
What is the mechanism by which glucose is reabsorbed from the filtrate into PCT cells?
Secondary active transport via sodium-glucose co-transport
Which transporters are involved in the reabsorption of glucose in the PCT?
Sodium-glucose co-transporter 2 (SGLT2) and sodium-glucose co-transporter 1 (SGLT1)
How does glucose exit PCT cells after being reabsorbed?
Facilitated diffusion through glucose transporter proteins (GLUT2 or GLUT1)
What type of transport mechanisms are used for amino acid reabsorption in the PCT?
Secondary active transport mechanisms involving sodium co-transporters
How are phosphate ions reabsorbed in the PCT?
Via sodium-dependent phosphate co-transporters
What role do Na+/K+-ATPase pumps play in phosphate reabsorption?
They generate a sodium gradient that allows phosphate to move against its concentration gradient
How are bicarbonate ions reabsorbed in the PCT?
Through the exchange of bicarbonate ions for chloride ions via the sodium-bicarbonate co-transporter (NBC)
What is the primary driving force for water reabsorption in the PCT?
Osmosis, driven by the reabsorption of solutes such as sodium and glucose
What happens to sodium ions after they are reabsorbed into PCT cells?
They are pumped out into the interstitial fluid and bloodstream by Na+/K+-ATPase pumps
How are potassium and chloride ions reabsorbed in the PCT?
Paracellularly along with water through passive diffusion
What is the first method for sodium reabsorption in the PCT?
Na+/K+ ATPase pumps sodium across the basolateral membrane and sodium enters the cell via transporters or channels across the apical membrane
What is the second method for sodium reabsorption in the PCT?
HCO3- combines with H+, is converted to CO2, which diffuses into the PCT cell
What is the role of carbonic anhydrase in sodium reabsorption?
It converts carbon dioxide to carbonic acid
What is the relationship between the two mechanisms of sodium reabsorption in the PCT?
They work hand-in-hand, with the sodium gradient driving water and electrolyte reabsorption
What is the main function of the early part of the PCT?
Reabsorption of solutes, nutrients, and bicarbonate
What does the latter part of the PCT primarily reabsorb?
Sodium, chloride, and water
How do sodium and chloride concentrations change along the length of the PCT?
They stay the same since water is reabsorbed at a nearly equimolar rate
Where are most organic solutes transported?
Only in the PCT
What happens if glucose and amino acids are not reabsorbed in the PCT?
They will not be reabsorbed further down the nephron and will be lost in the urine
What drives the reabsorption of most organic solutes?
Sodium gradient or negative membrane potential
What is the capacity of many transporters in the PCT?
Up to 100 different solute species
How are proteins like albumin and peptide/protein hormones degraded in the PCT?
Through a process of continuous endocytosis (pinocytosis)
How is glucose taken up across the apical membrane in the PCT?
By sodium-glucose symporters (SGLT family)
How does glucose leave the PCT across the basolateral membrane?
Via glucose uniporters (GLUT family)
What is the stoichiometry of sodium-glucose transport in most of the proximal tubule?
One-for-one
Which SGLT isoform is responsible for most glucose reabsorption?
SGLT-2 isoform
What is the stoichiometry of sodium-glucose transport in the late proximal tubule?
Two-for-one (SGLT-1 isoform)
When is glucose reabsorption saturated?
In the setting of significant (pathologic) hyperglycemia
What are organic cation and organic anion transporters known as?
OCTs and OATs, respectively
What do OCTs use to move cations from the bloodstream into the PCT cell?
The inside-negative membrane potential
What mechanism do OATs use to transport substances?
Countertransport
What role do principal cells play in the kidney?
Regulating sodium and water transport under the influence of aldosterone
What channels allow sodium ions to move into principal cells?
Epithelial sodium channels (ENaC)
How does aldosterone enhance sodium reabsorption?
By increasing the number and activity of ENaC channels
What creates an osmotic gradient that promotes water reabsorption?
Sodium reabsorption by principal cells
What channels allow water to move passively into principal cells?
Aquaporin-2 (AQP2) water channels
How does aldosterone indirectly enhance water reabsorption?
By promoting sodium reabsorption
What is the role of principal cells in potassium secretion?
They secrete potassium ions into the tubular lumen
How does aldosterone affect sodium-potassium pumps?
It stimulates their activity on the basolateral membrane
What is the major site of secretion of many general wastes/substances?
The PCT
What mechanisms are involved in the formation of dilute and concentrated urine?
Countercurrent exchange and multiplication mechanisms
What are the distinct histological characteristics of the loop of Henle?
Descending limb is permeable to water; ascending limb is impermeable to water but actively transports ions
What is the effect of the countercurrent multiplier system?
It amplifies the concentration gradient in the medulla
What does ADH do in relation to water reabsorption?
Increases permeability of collecting ducts to water
What do urea transporters contribute to in the medullary osmotic gradient?
Facilitating urea reabsorption in the collecting ducts
What is the role of the NKCC channel in the thick ascending limb?
Actively transports sodium, potassium, and chloride ions out of the tubule
What is a key action of angiotensin II?
Stimulates sodium tubular reabsorption
What stimulates the secretion of renin by JG cells?
Sympathetic input, pressure in the afferent arteriole, macula densa release
What does angiotensin II do in the vasculature?
Causes vasoconstriction
Where is angiotensinogen synthesized?
In the liver
What regulates the level of circulating renin?
Dietary sodium intake
What effect does low tubular sodium have on renin secretion?
Stimulates the release of renin
What happens to renin secretion when there is high vascular pressure?
It is suppressed
What is the primary function of the renin-angiotensin-aldosterone system (RAAS)?
Regulating renal sodium excretion
What does angiotensin II stimulate in the CNS?
Salt appetite, thirst, and sympathetic drive
What channels are inserted into the apical membrane of collecting duct cells by ADH?
Aquaporin-2 channels
What structure of the nephron maximizes the countercurrent exchange and multiplier mechanisms?
Hairpin loop structure
What is the role of vasa rectae in the medullary osmotic gradient?
Exchanges ions and water with the surrounding interstitium
What is the effect of constricting both cortical and medullary vessels in the kidney?
Reduces total renal blood flow and decreases GFR, thus decreasing the filtered load of sodium.
What are ACE inhibitors used for?
They reduce the production of AT2.
What does aldosterone stimulate in the nephron?
Sodium reabsorption in both the proximal tubule and distal nephron.
Which sodium transporters are stimulated by aldosterone in the proximal tubule?
- NHE3 sodium/hydrogen antiporter
- Na-K-ATPase
What is the role of NCC in the distal tubule?
It is a sodium/chloride symporter that imports sodium.
What is a major stimulator of sodium reabsorption in the distal nephron?
Aldosterone.
What happens to aldosterone in the presence of elevated AT2 levels?
It promotes the activity of luminal NCC sodium/chloride symporters in the distal tubule.
True or False: Aldosterone is effective at stimulating NCC activity without AT2.
False.
What are the cellular targets of aldosterone?
Cells in the distal tubule and beyond.
How does aldosterone act on tubular cells?
It combines with mineralocorticoid receptors in the cytoplasm.
What is the consequence of aldosterone binding to its receptor?
It promotes gene expression of specific proteins.
What is the role of aldosterone in other epithelial tissues?
Stimulates sodium transport in sweat and salivary ducts and the intestine.
What segments of the nephron are involved in calcium and phosphate transport?
- Proximal Convoluted Tubule (PCT)
- Thick Ascending Limb of the Loop of Henle
- Distal Convoluted Tubule (DCT) and Connecting Tubule (CNT)
- Collecting Duct (CD)
How is calcium reabsorbed in the PCT?
- Paracellular pathways via passive diffusion
- Transcellular pathways via calcium channels and transporters
What transporters facilitate phosphate reabsorption in the PCT?
Sodium-dependent phosphate co-transporters.
What occurs in the thick ascending limb regarding calcium?
Minimal calcium reabsorption occurs mainly through paracellular pathways.
What is the role of PTH in the DCT and CNT?
Stimulates calcium reabsorption by increasing calcium channel activity.
What is the phosphate handling in the DCT and CNT?
Minimal reabsorption; primarily phosphate secretion.
How do hormones like PTH and calcitonin affect calcium handling in the CD?
They modulate the activity of calcium channels and transporters.
What is the main process for phosphate excretion?
Occurs in the urine under the influence of PTH and FGF23.
What is the primary function of buffer systems in the body?
To maintain acid-base homeostasis by minimizing changes in hydrogen ion (H+) concentration.
List the major buffer systems in the body.
- Carbonic Acid-Bicarbonate Buffer System
- Protein Buffer System
- Phosphate Buffer System
- Ammonia Buffer System
- Bone Buffer System
Where is the Carbonic Acid-Bicarbonate Buffer System primarily located?
In the extracellular fluid (ECF), including blood plasma.
What is the importance of the Carbonic Acid-Bicarbonate Buffer System?
It is one of the most important regulators of blood pH, involving the reversible reaction between carbonic acid (H2CO3) and bicarbonate ions (HCO3-).
How do protein buffers function?
They contain amino acid residues that can accept or donate H+ ions, helping to maintain pH stability.
Where is the Phosphate Buffer System primarily found?
In the intracellular fluid (ICF) and renal tubular fluid.
What role do phosphate ions play in the Phosphate Buffer System?
They act as weak acids and bases, buffering changes in pH by accepting or donating H+ ions.
Where is the Ammonia Buffer System primarily located?
In the renal tubular fluid and urine.
How does the Ammonia Buffer System function?
Ammonia (NH3) accepts H+ ions to form ammonium ions (NH4+), regulating urinary pH.
What is the significance of the Bone Buffer System?
Bone acts as a reservoir for alkaline salts that can neutralize excess H+ ions in the bloodstream.
What is the first task of the kidneys in acid-base balance?
To reabsorb most of the filtered bicarbonate.
Where does the reabsorption of bicarbonate primarily occur?
In the proximal tubule.
What is the major route for bicarbonate reabsorption?
An acid-base process involving the secretion of hydrogen ions.
What enzyme catalyzes the generation of hydrogen ions and bicarbonate from CO2 and water?
Carbonic anhydrase.
How do hydrogen ions get secreted into the tubular lumen?
In exchange for sodium via an antiporter or via a primary H-ATPase.
What is the role of the Na-H antiporter (NHE3) in the proximal tubule?
It mediates hydrogen ion secretion and sodium uptake.
What defines glomerulotubular balance?
The intrinsic ability of renal tubules to adjust their reabsorption rates according to changes in the filtered load.
How does hydrostatic pressure in the peritubular capillaries affect reabsorption?
Higher hydrostatic pressure facilitates the reabsorption of water and solutes.
What metabolic processes generate acids in the body?
- Carbohydrate metabolism
- Fat metabolism
- Protein metabolism
What is the fruit juice paradox in terms of metabolism?
The metabolism of acidic substances like citrus fruit can alkalinize the blood.
What condition can renal diseases lead to regarding acid-base balance?
Acidosis due to impaired excretion of hydrogen ions or reabsorption of bicarbonate.
What is renal tubular acidosis?
A condition that impairs the kidneys’ ability to excrete acid or regenerate bicarbonate.
What triggers compensatory responses in acid-base physiology?
Disruptions in acid-base physiology
What is the renal response to acidosis?
Increase reabsorption of bicarbonate ions (HCO3-) and increase secretion of hydrogen ions (H+)
What is the renal response to alkalosis?
Decrease bicarbonate reabsorption and decrease hydrogen ion secretion
How does the respiratory system respond during acidosis?
Increases the rate and depth of breathing (hyperventilation)
What effect does hyperventilation have on blood CO2 levels?
Decreases CO2 levels
What is the respiratory response during alkalosis?
Decreases respiratory rate and depth (hypoventilation)
What happens to CO2 levels during hypoventilation?
Increases CO2 levels
What are the two main compensatory mechanisms for acid-base balance?
- Renal response
- Respiratory response
Which compensatory response occurs more rapidly?
Respiratory response
Which compensatory response is slower but more powerful?
Renal response
What are the four categories of acid-base disorders?
- High pCO2: respiratory acidosis
- Low pCO2: respiratory alkalosis
- Low bicarbonate: metabolic acidosis
- High bicarbonate: metabolic alkalosis
What is the Henderson-Hasselbalch equation used for?
To show the relationship between pH, bicarbonate, and PCO2
What indicates a primary uncompensated disorder?
Change in either PCO2 or bicarbonate concentration
What happens in respiratory acidosis due to low alveolar ventilation?
Increase in PCO2 and decrease in pH
How do healthy kidneys respond to increased PCO2 in respiratory acidosis?
Contribute new bicarbonate to the blood
What occurs in respiratory alkalosis regarding PCO2?
Decreased PCO2 and increased extracellular pH
What is the renal response to metabolic acidosis?
Produce more bicarbonate to return pH toward normal
How do kidneys respond to an acid load?
Reabsorb all filtered bicarbonate and increase formation and excretion of NH4+ and titratable acid
What indicates that kidneys are the cause of acid-base imbalance?
Bicarbonate concentration remains low despite renal response
Fill in the blank: In respiratory alkalosis, bicarbonate is _______ from the body.
lost
