Patho Midterm

the cellular changes that occur with glomerular disease include

1. Poliferation: increase in cellular components of the glomerulus

2. Sclerotic: increase in non-cellular components of the glomerulus

3. membranous: increase in the thickness of the glomerular capillary wall, often caused by immune complex deposition

acute postinfectious glomerulonephritis

• The most common form is “diffuse proliferation GN” after infection by group A beta-hemolytic strep

• Inflammation results from an immune rxn that occurs when circulating immune complexes become trapped in the glomerular membrane

• The capillary membrane swells and becomes permeable to plasma proteins and blood cells

• 95% of children and 60% of adults fully recover

acute postinfectious glomerulonephritis onset

7-12 days after strep infection → oliguria, proteinuria and hematuria (cola colored urine early sx) → sodium/water retention lead to edema (face and hands) and HTN

rapidly progressive glomerulonephritis

• clinical syndrome with rapidly progressing signs of severe glomerular injury that does not have a single specific cause (develops within months)

• E.g. Good Pasture’s syndrome causes 5% of RPGN, it is due to the production of antibodies to the glomerular basement membrane (also associated. with pulmonary hemorrhage, and iron deficiency anemia)

nephrotic syndrome

• A group of clinical findings that are due to increased glomerular permeability to plasma proteins

• may be primary disorder or secondary to changes caused by systemic disease, such as SLE, DM, etc

• characterized by “massive” proteinuria (>3.5 g/day) lipiduria, hypoalbuminemia, generalized edema, and hyperlipidemia (high lipoproteins as liver tries to compensate for protein loss)

• other effects of protein loss include dyspnea due to pulmonary edema, pleural effusions, ascites, compromised immunity, increased risk of thrombosis and arthrosclerosis

wilm’s tumor (nephroblastoma)

• very common neoplasm of young children

• may occur in any part of the kidney

• grow to large size distorting kidney structure

• can be exercised in early stages but may eventually matastasize to lungs

• commonly presents with large abdominal mass and hypertension (may be abdominal pain vomiting or both)

• long term survival of 90% with agressive treatment plan

adult kidney cancer

• 2% of all cancer incidence and mortality in U.S.

• 80-85% of adult kidney cancer is renal cell CA

• affects elderly (men 2x as women)

• Some may arise due to chronic irritation from kidney stones or smoking (other risk factors include: obesity, exposure to petroleum products, asbestos and heavy metals; cystic kidney disease)

• symptoms generally present only with advanced disease (hematuria, costovertebral pain, palpable flank mass, polycythemia and fever)

• 5-year survival depends on stage of progression (from 65-85% for stage I to 0-10% for stage IV)

types of renal failure

1. Acute renal failure

2. chronic renal failure

3. uremia

acute renal failure

• a rapid decline in GFR (< 20% of normal), with a resultant increase in blood urea nitrogen and serum creatinine levels (“azotemia”)

• may result from damage to any portion of the kidney, or extra-renal lesions (e.g. bilateral lower UT obstruction) and is a frequent complication of hypotensive shock

chronic renal failure

• end-stage renal disease, with is characterized clinically by “uremia” = “urine in the blood” (the syndrome associated with chronic azotemia)

• results from a variety of serious kidney diseases

uremia

• Few symptoms appear until > 67% of nephrons have been destroyed, then virtually every organ and structure is affected

• disorders of water (dehydration or over hydratio), electrolytes (na/K) and acid-base balance (metabolic acidosis)

• mineral and bone disorders (anemia and coagulopathies)

• cardiovascular disorders (HTN, CHF, etc.)

• GI neurological and immune systems; and skin all negatively affected

covid 19 pandemic

• Novel strain of coronavirus (same family of virus that can cause common cold) identified in December. 2019

• began in Wuhan, China but rapidly spread to the middle eat, Europe and beyond

• seems to cause mild symptoms in most people under the age of 65 but the death rate increases dramatically with age (overall about 1-3% but 10-120% in those over 80n

• at least 90,000 cases in Nb to date (about 900 deaths) now in the “6th wave” related to the BA2 subvariant of Omicron

• vaccine rollout ongoing and antivirals available to some

the swine flu (H1N1) pandemic

• novel strain of influenza (to humans) as of April 2009 (pigs)

• affected more “young and healthy” adults than regular seasonal flu, but symptoms were usually mild

• greater risk in pregnancy (for mom)

severe acute respiratory syndrome (SARS)

• caused by novel coronavirus identified in 2003 (bats to cats?)

• risk is very low for the average Canadian

• death rate was approx. 10% (higher in elderly)

infuenza virus

• rarely fatal → flu shots

• type A most common and more severe than B

• abrupt onset of fever chills malaise muscle aching headache nasal discharge cough and sore throat (rhinotrachetitis) → resolves in 7-10 days

3 types of influenza virus

1. rhinotracheitis

2. Respiratory viral infection followed by a bacterial infection

3. viral pneumonia / avian flu

adenovirus

• can cause inflammatoon of the brinchioles (acute bronchiolotis) and healing by fibrosis

• peak from 3-6 months of age (usu. <2 y.o.)

• wheezy cough, dyspnea, and irritability

• rare progression to respiratory failure in infants

• also cause common cold, croup and pneumonia

respiratory syncytial virus (RSV)

similar to adenovirus but more frequent association with epidemics in nurseries, hospitals, etc.

Bordetella pertussis = bacterium that causes “whooping cough” (pertussis)

• highly contagious infection of upper RT in children

• rare after intro of vaccine but early vaccines undafe (many adverse reactions)

three stages of Bordetella pertussis = bacterium that causes “whooping cough” (pertussis)

1. catarrhal: fever sneezing runny nose and dry cough

2. paroxysmal: paroxysmal coughing with deep inspiration followed by series of quick short coughs, ending with long shrill whooping inspiration due to spasmodic closure of the glottis (3-4 wks)

3. convalescent: gradual recovery

atelectasis

• = collapse of expanded lung tissue

• air supply obstructed → trapped gases gradually diffuse from expanded alveoli to blood → collapses region of lung tissue beyond obstruction

• important post operative complication of abdominal surgery → mucous obstructs bronchus → may be asymptonatic or resukt in hypoxia and/or bronchiectasis

bronchiectasis

• = irreversible dilation of bronchi following destruction of the muscular and elastic elements of their walls

• may result from mechanical obstruction of the central bronchi by inhaled foreign bodies, tumours, mucous plugs etc/ (localized)

• usually a complication of respiratory infections (50-67%) or defects in immune mechanisms (more generalized damage)

pneumonia

• acute inflammation and consolidation (solidification) of the pulmonary parenchyma (bacterial and viral forms)

  • lobar: consolidation of entire lobe

  • bronchopneumonia: scattered solid foci remains a common cause of death in terminally ill

• numerous conditions predispose to infection by depressing host defenses, influding

  • cigarette smooking chronic bronchitis alcoholism malnutrition/wasting diseases poorly controlled diabetes

bacterial pneumomia

affect alveoli and interstitium

pneumococcal (strep pneumoniae)

• most common cause of pneumonia (90%); esp lobar pneumonia

• frequently follows viral infections (e.g. influenza)

• onset: high fever/chills → chest pain, hemoptysis (rusty sputum) resolves with abx

• complication include: painful pleuritis pleural effusion empyema bacteremia (→ endocarditis/meningitis), pulmonary fibrosis, and lung abscess

klebsiella

• only other significant cause of lobar pneumonia

• commonly associated with alcoholism and middle-aged men

• high mortality rate despite abx tx

straphylococcal (staph, aureus)

• following other viral infections (e.g. influenza)

• repeated episodes in CF pts

• frequent development of pulmonary abscesses

legionella

• first outbreak at american legion convention in philadelphia in 1976

• thrives in stagnant water (e.g. a/c cooling towers, construction sites)

• infectious byt not contagious

• onset acute with malaise fever muscles aches and abdominal pains → productive cough and rarely chest pains die to pleuritis

• high mortality rate especially among elderly and immunocompromised

psittacosis

• results from inhalation of chlamydia psittaci in dust contaminated from birds (usually pet parrots)

• severe systemic symtoms of fever malaise muscle aches but few respiratory symptoms besides a cough

• fatal cases involve varying degrees of diffise alveolar damage edema intra alveolar pneumonia and necrosis

types of bacterial pneumonia

1. pneumococcal (strep pneumoniae) (90%)

2. Klebsiella (1%)

3. staphylococcal (1%)

4. legionella (legionnaires dz)

5. C. psittaci

viral pneumonia

• produce interstitial (not alveolar) pneumonia and diffuse alveolar damage

• may be caused by: CMV, measles and varicella infections

• generally resolves completely rarely progresses to interstitial fibrosis

mycoplasma pneumoniae

• cause the syndrome of atypical pneumonia

• onset insidious and respiratory symptoms minimal

• course prolonged and only rarely fatal

• AKA “walking pneumonia”

lung abscesses

localized accumulation of pus accompanied by destruction of the pulmonary parenchyma (alveoli, airways, and blood vessels)

causes of lung abscesses

• The most common cause is aspiration of bacteria from the oral cavity, often in the setting of altered consciousness. → alcoholism is a most common predisposing condition (also drug overdose, epilepsy, and neurological impairment)

• Other causes include: pneumonia, bronchial obstruction, pulmonary infection, pulmonary embolism, penetrating wound, and extension of infection from adjacent tissue

lung absecess clinical features

• cough and fever

• large amounts of foul smelling sputum

• pleuritic chest pain and hemoptysis (20%)

Complications of lung abscess

• empyema (after rupture of abscess into pleural space), or drainage into bronchus→ dissemination to other parts of lung

• mortality 5-10% despite treatment with antibiotics

Diffuse alveolar damage (DAD)

reaction of distal pulmonary tissue to a variety of insults that injure epithelial and endothelial cells of the alveoli, characterized by interstitial inflammation and proteinaceous alveolar exudate (leaks though damage endo)

causes of DAD

• viral URTI

• sepsis

• shock

• aspiration of gastric contents

• inhalation of toxic gases

• near drowning

• radiation

• drugs

• chemicals

Adult respiratory distress syndrome (ARDS)

• clinical presentation of DAD

• patient with previously normal lungs suffers damage —> rapidly progressive respiratory failure

DAD (and ARDS) clinical features

• symptom-free period for up to several hours after “insult” → tachypnea and dyspnea → cyanosis →

  1. gradual improvement of full recovery

  2. recovery with scarring, permanent respiratory dysfunction and/or pulmonary hypertension

  3. fatality

• mortality > 50% (90% in patients over 60 yoa)

chronic obstructive pulmonary disease (COPD)

non specific term that describes patients with chronic bronchitis or emphysema who show evidence of decreased forced expiration volume (FEV) as measured bu spirometric pulmonary functions tests

types of COPD

1. chronic bronchitis

2. emphysema

chronic bronchitis

• clinical defined as the presence of a chronic productive cough without a discernible cause for more than 50% of a 2 year period

• 90% of cases occur in smokers

• characterized by hyperplasia and hypertrophy of mucous secreting cells and increased proportion of mucus to serous cells

clinical features of chronic bronchitis

• often accompanied by emphysema, it is difficult to separate the relative contribution of each to sxs

• productive cough for many months/ years, particularly during winter months

• exertional dyspnea (DOE), cyanosis, and cor pulmonale (with edema) may develop→ “blue bloater”

emphysema

• progressive enlargement of the air spaces distal to the terminal bronchioles with destruction of their walls

• rare in nonsmookers (only 1% of all cases due to hereditary deficiency in alpha1-antitrypsin→ inhibits enzyme, elastatse, that otherwise destroys elastic CT in lungs)

emphysema clinical features

• usually elderly with long history of DOE but with minimal non productive cough

• tachypnea and prolonged expiratory phase (overinflation of lungs → “barrel chest”)

• no cyanosis → “pink puffers” no treatment

why does emphysema cause a decline in respiratory function

1. loss of elastic recoil → reduced force of expiration (plus collapse of airways) so air remains trapped inside lungs

2. loss of pulmonary surface area for exchange of gases

astma

a respiratory condition characterized by variable obstruction to the flow of air and increased airways responsiveness to various stimuli. Clinically, patients exhibit paroxysms of wheezing, dyspnea and cough

in U.S. bronchial asthma affects

• > 10% of children

• 5% of adults

• (1/2 of all cases are in pts <10 yoa; girls 2x as often as boys)

allergic asthma

• The most common form

• allergens include pollens, animal hair or fur, and contamination of house dust with mites

other triggers of astma attacks

• viral infections in children

• exercise induced asthma (bronchospasm in response to rapid, cold air movement)

• occupational asthma = allergic? (bakers, pharmacists, animal handlers, etc)

• drug induced (e.g. aspirin)

• air pollution (e.g. smog)

• emotional factors/psychological stress

asthma triggers release various inflammatory mediators that result in

1. Immediate response

2. delayed response

immediate response

• smooth muscle contraction

• mucus secretion

• increased vascular permeability → edema of the walls of the bronchi

delayed response

epithelial cell injury that may stimulate nerve endings in the mucosa → autonomic discharge → further airway narrowing and mucus secretion

clinical features of asthma

• inspiratory and expiratory wheezes

• increased respiratory rate and dyspnea

• prolonged expiration

• end of attack heralded by severe coughing and expectoration

• “status asthmaticus”

status asthmaticus

increasingly severe attack that does not respond to drugs (potentially life-threatening)

why does body respond to hypoxia by constricting pulmonary arteries servicing underperfused areas of the lung

to shunt blood to region of optimal gaseous exchange

_____ if a small area of lung is hypoxic, but _____ if generalized hypoxia is occurring → worsens the problem

• adaptive

• maladaptive

carcinoma

• The most common cause of death from cancer in U.S. and Canada

• second most common form of cancer in men (to prostate)/ women (to breast)

• 90% of lung cancers are consequence of cigarette smoking

• metastasis to regional lymph nodes, adrenal glands, brain, bone and liver is common

squamous cell carcinoma

• 30% of all invasive lung cancers in the U.S.

• Most arise from the central portion of the lung (bronchi)

• usually present with persistent cough, hemoptysis and/or bronchial obstruction (with associated pulmonary infections or atelectasis)

• Pleural effusion commonly leads to dyspnea

• may result in compression of SVC → upper body venous and lymphatic congestion (SVC syndrome)

nerve involvement of squamous cell carcinoma

Involvement of cervical and thoracic nerves (= pan coast tumour may result in shoulder pain radiating in ulnar distribution down the arm and/or Horner syndrome → eyelid ptosis, pupillary constriction, and absence of sweating on one side (asymmetrical anhydrosis))

survival rate or squamous cell carcinoma

• median survival time < 1 year if untreated

• Fortunately, at the time of diagnosis, 60% of tumours are deemed to be resectable, and 5-year survivorship following surgery is 37%

adenocarcinoma

• 33% of all invasive lung cancers

• most arise in periphery of lungs

• grow more rapidly than SCC and frequently invade the pleura

• less than 40% can be resected at disease, and 5-yr survival only 25%

small cell carcinoma

• 20% of all lung cancers

• usually originates near the hilum of the lung

• 67% already have metastasis to various organs at the time of disease (highly malignant)

• 2 to 4 months survival w/o treatment

• despite recent improvements in prognosis due to advances in chemotherapy, overall cure rate remains low (5-10% survival at 5 years)

like the bone the most common malignant neoplasm of the lung is

• the metastatic tumour

• primary sites of cancer are most typically the breast, stomach, pancreas and colon

pleura pathologies

1. pneumothorax

2. pleural effusion

pneumothorax

presence of air in the pleural cavity

types of pneumothorax

1. traumatic

2. spontaneous

3. tension pneumothorax

traumatic pneumothorax

penetrating wounds (stab/rib fracture) or following surgical procedures

spontaneous pneumothorax

typically in tall, thin, male, young adults while exercising → acute chest pain and SOB → may subside on own or require “dainage”

tension pneumothorax

severe unilateral pneumothorax that causes mediastinum to shift to opposite side and compress the “good lung” → medical emergency → immediate removal of air is required

pleural effusion

accumulation of excess fluid in the pleural cavity

pleural effusion types

1. hydrothorax

2. pyothorax

3. empyema

4. hemothorax

5. chylothorax

hydrothorax pleural effusion

Watery effusion is due to increased hydrostatic pressure within capillaries (e.g. heart failure)

pyothorax pleural effusion

turbid effusion (pus) that commonly occurs as a complication of bacterial pneumonia

empyema pleural effusion

as above (pyothorax, hydrothorax), with thicker pus

hemothorax pleural effusion

blood as a result of trauma or rupture of blood vessel

chylothorax pleural effusion

milky, lipid-rich fluid (chyle) as a result of lymphatic obstruction (poor prognosis)

cystic fibrosis

• the most common fatal hereditary disorder in whites in U.S. and most common cause of chronic lung disease in children

• autosomal recessive disorder → reduced chloride transpot across memebranes of epithelial cells → unusally thick fluid secrertion in exocribe glands and epithelial lining of RT, GIT and GUT → results in obstruction of organ passages (e.g. airways and pancreatic ducts

cystic fibrosis also manifests as

1. chronic respiratory disease

2. pancreatic exocrine deficiency (maldigestion)

3. elevation of NaCl in sweat

4. also common

   • nasal polyps

   • sinus infections

   • pancreatitis

   • cholelothiasis

   • salt depletion / electrolyte imbalance

   • azoospermia (infertility in males)

cystic fibrosis respiratory manifestation cause by

1. Accumulation of viscus mucus in the bronchi

2. Impaired mucociliary clearance

3. repeated lung infections

   • initially, chronic bronchiolitis and bronchitis

   • structural changes in the bronchi wall lead to bronchiectasis → cysts and abscesses

   • lung destruction from infection and inflammation

   • Early diagnosis and symptomatic treatment (bronchodilators, pancreatic enzymes, chest percussion, prompt treatment of infection) are important in delaying the onset and severity of chronic illness