Exam 2 Flashcards
Path of O2 in airway
o Alveolar Epithelium ->
o Fused basement membranes ->
o Capillary endothelium ->
o CO2 goes in reverse (20x more diffusible than O2)
Normal Structure Alveolar epithelium
Pneumocytes o Type 1: • Squamous • little repaire • no regen o Type 2: • Cuboidal, microvilli • Can regen • Produce surfactant
Normal structure bronchioles
o Clara cells act as stem cells
o Used for enzymatic detox
Nutritional Vs Functional blood supply in lungs
o Functional
• From R heart for gas exchange
o Nutritional
• From L heart to interstitial tissue in lungs
Ventilation / perfusion mismatch
o Blood & air are not getting to same place
o Due to block of blood supply or block of airway
Acid Base Balance in lungs
Respiratory alkalosis
• due to HYPERventilation = blow off CO2
Respiratory Acidosis
• due to HYPOventilation = too much CO2
Metabolic Acidosis
• Respiratory compensation: HYPERventilation
Metabolic Alkalosis
• Respiratory compensation: HYPOventilation
Define: tachypnea, dyspnea, cyanosis, hemoptysis, epistaxis, stridor, stertor
o Tachypnea- rapid breathing o Dyspnea - labored breathing o Cyanosis - blue skin due to decreased blood O2 or circulation o Hemoptysis – coughing blood o Epistaxis – nose bleed o Stridor - harsh grating sound o Stertor - snoring
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3 Routes of entry of organisms into lungs, & natural defenses for those routes
Inhalation (airborne) • Sneezing, coughing, bronchoconstriction • Mucociliary clearance • Phagocytosis by alveolar macrophages • Hyperplasia = chronic resp Dz
Hematogenous (blood borne)
• Intravascular macrophages
Direct Extension (penetrating)
Primary Ciliary Dyskinesia
o Genetic defect in ciliary morphology ->
o Defective ciliary movement ->
o Defective mucociliary clearance ->
o Predisposition to infection
Defenses against blood-borne respiratory agents in dogs & rodents Vs ruminants, cats, pigs, horses
Dogs, rodents, humans
• phagocytosed by Kupffer cells and splenic macrophages
ruminants, cats, pigs, horses
• pulmonary intravascular macrophages
4 Main Causes of Impairment of Respiratory Defenses
Viral:
• Destruction of cilia,
• impaired pulmonary alveolar macrophage function
• often predisposes to bacterial infection
Bacterial:
• Inhibit cilia,
• survival and replication in macrophages
• can predispose to other bacteria
Toxic gasses:
• Direct injury to tracheal/bronchial epithelial cells and pneumocytes
Immunodeficiency:
• not very common
Cellular Response to Acute & Chronic Mucosal Damage in Respiratory Tract
Acute Mucosal damage:
• Decreased cilia + increased goblet cells
• Inflammation - hyperemia, edema, neutrophils
• Impaired mucociliary clearance
• Ciliated epithelium will repair IF basement membrane is intact or scar if not
Chronic Mucosal Damage • Goblet cell hyperplasia • Fibrosis • Squamous metaplasia • Decreased clearance and increased airway resistance
Cellular Response to Smooth Muscle, Alveoli, & Interstitium Damage in Respiratory System
Smooth Muscle
• Hyperplasia/hypertrophy of smooth muscle = increased airway resistance
Alveoli
• Type II pneumocyte hyperplasia = reduced gas exchange
Interstitium
• Interstitial fibrosis = reduced ventilation of alveoli
Developmental Abnormalities of the nasal cavity & sinuses
brachycephalic dogs:
• Noisy inspiration
• May have obstruction w/ cyanosis and collapse during exercise
• Elongation of soft palate causing obstruction of glottis -> increased inspiratory effort.
Cleft palate
• Milk and food from nostrils = sneezing, nasal discharge
• Associated with aspiration pneumonia.
Atrophic Rhinitis: predisposing factors, offending agents, pathogenesis
Predisposing factors: • infectious (bacteria +/- viral), • environment, • genetics, • nutrition
Agent
• Bordatella bronchiseptica + Pastuerella multocida
Pathogenesis:
• Toxins from Pasteurella stimulate osteoclasts & inhibit osteoblasts -> degeneration and remodeling of nasal turbinates
Epistaxis: 3 places it may originate & causes
Blood may originate from w/in nasal cavity
• Causes: Trauma, inflammation, ethmoid hematoma
Blood may originate distal to the nasal cavity
• Causes: Guttural pouch mycosis, neoplasia, pneumonia, exercise-induced pulmonary hemorrhage in horses
Blood may not necessarily be due to local disease
• Causes: Platelet / coagulation defects
Nasal Cavity Neoplasias: most common types in dogs, cats, & sheep
Most common in dogs & most are malignant
• nasal carcinoma/adenocarcinoma
Cats
• squamous cell carcinoma, lymphoma
Sheep
• Enzootic nasal carcinoma (retrovirus)
Non-neoplastic Nodules in Nasal Cavity
- Nasal polyps (cat/horse)
* Cysts (horse)
Equine pharyngeal lymphoid hyperplasia: basics, signs, gross lesions, histo
- Most common cause of partial upper airway obstruction in horses (esp 2-3 yr old racehorses, 30- 60%)
- Regress with age
- Etiology unknown: likely chronic bacteria + environment
Signs
• Stridor, changes in voice, dysphagia, cough, dyspnea in severe cases
Gross Lesions
• White foci in dorsolateral pharynx
Histo
• Lymphoidnodules
Brachycephalic airway syndrome
- Stenotic nare and elongated soft palate -> laryngeal edema
- Can have severe upper airway obstruction
- Common in Bulldogs, boxers, boston terriers, pugs, Pekinese
- Signs: Sturdor (snoring), exercise intolerance, +/- severe dyspnea, cyanosis
Necrotic Laryngitis
- Aka laryngeal necrobacillosis or calf diphtheria
- Calves: damage to laryngeal mucosa (feed, balling gun) - > Secondary bacterial infection -> Local inflammation/necrosis, risk of pneumonia, risk of local airway obstruction
Laryngeal hemiplagia
• AKA roaring
Horses
• Atrophy of dorsal and lateral cricoarytenoid muscles
• Denervation due to primary or secondary disease of left recurrent laryngeal nerve -> affects L side
Dogs
• Laryngeal paralysis
Neoplasia affecting pharynx/larynx
Dogs: very rare tonsilar squamous cell carcinoma
Issues w/ guttural pouch
Guttural pouch Tympany
• distention with fluid and gas
Guttural Pouch Empyema
• distention with purulent exudate
Guttural pouch Mycosis
• fungal infection
Guttural Pouch Mycosis: entry, lesion, signs
- fungal infection
- Most common problem with the guttural pouch
- Usually unilateral
Entry
o Inhalation of mold spores from feed/environment
Lesion
o Fibrinonecrotic exudate- necrosis and inflammation
Signs
o Epistaxis- Unilateral or bilateral, acute or intermittent
o Nerve damage
Disease & Other Causes of inflammation in trachea
- Canine Infectious tracheobronchitis
- Herpes viruses - Infectious Bovine Rhinotracheitis, Equine Rhinopneumonitis
- Secondary to collapsing trachea, other trauma
Signs of tracheal inflammation
- Non-productive honking cough
* Obstruction (in birds)
Tracheal anomalies
- Agenesis
* Hypoplasia (bulldogs)
Tracheal collapse: cause & signs
- Wide dorsal tracheal membrane
- Small breed dogs
Causes:
• Trauma, obesity, masses may exacerbate
Signs • Dry, honking cough • Dyspnea (worse with stress/exercise) • Cyanosis • +/- secondary pneumonia
Restrictive Respiratory Failure
- Pathology that results in restriction of inflation of the lungs
- Intrapulmonary
- extrapulmonary
Pathophysiology • Restriction of lung inflation limits ventilation -> • Low O2 Normal CO2 -> • Rapid, shallow respirations -> • Low CO2 -> • respiratory alkalosis
Intrapulmonary Restrictive Respiratory Failure
Lesions in alveolar and interlobular septa o Interstitial edema o Interstitial pneumonia o Alveolar Fibrosis o Type II pneumocyte hyperplasia
• Effect is less compliant walls
Extrapulmonary Restrictive Respiratory Failure
Lesions in pleural cavity, mediastinum, thoracic wall
o Pleural effusion (fluid in pleural cavity)
o Pneumothorax
(air in pleural cavity)
o Deformities (or masses)
Obstructive Respiratory Failure: pathophysiology & mechanisms
• Pathology that results in reduced ventilation of the lungs
Pathophysiology • Obstruction of air flow in lungs reduces ventilation -> • Low O2 & High CO2 -> • Rapid/deep respiration -> • Low O2 High CO2 -> • respiratory acidosis
Mechanisms
• Obstruction of movement of air in airways or alveoli
• Exudative pneumonia- exudates fill alveoli
• Pulmonary edema – edema in alveoli
• Bronchitis or bronchiolitis- exudates, mucous, hyperplastic epithelium obstructs airways
Recurrent Airway Obstruction (RAO, Heaves)
- Horses
- Likely allergic
- Diffuse bronchiolitis - epithelial hyperplasia, mucous
Signs o Cough o Tachypnea o Wheeze o Exercise intolerance o Dyspnea- Expiratory -> “heave line” o Weight loss
Feline Asthma: pathogenesis, respiratory signs, other signs
Pathogenesis
o Obstruction of small airways
->
o Bronchiolar smooth muscle hyperplasia and constriction
o Hypertrophy/hyperplasia of mucous glands
Respiratory signs
o Normal at rest
o Coughing to severe respiratory distress when stressed
o Lung sounds normal to crackles and wheezes
Other signs:
o Anorexia, weight loss
o Peripheral eosinophilia in 30%
Pulmonary Edema: Pathogenesis & mechanisms
Pathogenesis:
• Fluid accumulates in the interstitium restricts lung inflation
for variable length of time
->
• Fluid in alveoli occurs abruptly
->
• Increased rate and depth of respiration
->
• Loud lung sounds initially (quiet with severe edema)
Mechanisms
• Increased permeability
• Increased hydrostatic pressure or Decreased oncotic pressure
• Impaired lymphatic drainage
Increased Permeability leading to pulmonary edema
- cytokines -> inflammation ->
- damage to pneumocytes & endothelium ->
- leaky vessels -> high protein fluid
Hemodynamics of pulmonary edema
Increased Hydrostatic Pressure
o Left heart failure - cardiogenic edema
o Hypervolemia/fluid overload
Decreased Oncotic Pressure
o Hypoalbuminemia
Impaired Lymphatic drainage in pulmonary edema
- Least common mechanism
* Neoplasia blocking lymphatics
Acute Respiratory Distress Syndrome (ARDS): symptoms, pathogenesis
• Diffuse damage to alveolar wall
Symptoms
o Sudden onset of severe dyspnea, tachypnea
Pathogenesis
o Activation of pulmonary macrophages ->
o Cytokine Release
->
o Stimulation of neutrophils – release enzymes + free radicals ->
o Damage to endothelium and alveolar epithelium ->
o Severe Edema
Atelectasis
• Collapse or incomplete expansion of alveoli
Congenital:
• Failure of lungs to expand at birth
Acquired
• Restrictive - pressure on lungs - > fibrosis
• Obstructive - collapse distal to obstruction due to resorbed fluid
Emphysema
- Emphysema- air trapped in alveoli or interstitium
- Reduced ventilation -> ventilation/perfusion mismatch
- Expiratory dyspnea
- Hypoxia and hypercapnia
Pulmonary Hypertension
• Increased pulmonary vascular resistance
Causes
• Vasoconstriction
• Vascular obstruction
• Vascular volume overload
Usually secondary to other dz
• Cardiac dz, lung dz, thromboembolism, hypervolemia
Cellular Changes in Pneumonia
Fibrin
o Sign of acute severe injury
Neutrophils
o Predominate with most bacterial infections
Macrophages
o Alveolar macrophages come quickly
o More macrophages with chronicity
Alveolar septal response to Pneumonia
Acute
o Edema and leukocytes in the interstitium
Chronic
o Squamousmetaplasia
o Fibrosis
o Non-suppurative inflammation
Transient Vs Chronic Injury in pneumonia
Transient Injury
• Complete repair in <1wk
Chronic Injury
• Fibrosis (restricts alveoli)
Classification of pneumonia
Etiology
o bacterial, viral, parasitic, toxic
Type of inflammation
o Suppurative
o Fibrinous
o granulomatous
Distribution o Cranioventral - o Lobar o Diffuse o multifocal
Morphologic type
o Broncho
o Interstitial
o bronchointerstitial
Distribution of Pneumonia
- Multifocal - granulomatous
- Lobular (ruminants)
- Lobar – usually cranioventral
- Dorsocaudal - parasitic
- Diffuse
Bronchopneumonia; facts, Resp signs, Systemic signs
- Most common pneumonia
- Origination of inflamm @ bronchiolar-alveolar junction
- Aerongenous
- Bacterial
- Cranioventral
Respiratory Signs o Productive cough o Tachypnea o Dyspnea o Wheeze o Exercise intolerance
Systemic Signs o Lethargy o Anorexia o Fever o Weight loss o Rough coat
Suppurative Bronchopenumonia
o Obstructive due to exudates
o Often bilateral, cranioventral (lobar), or lobular
o Acutely lungs are swollen and consolidated
o Over time exudates resolve, lung often atelectatic
Fibrinosuppurative Bronchopneumonia; basics, histo
o more severe than suppurative o lobar pattern o Protypical example: Shipping fever o Can be caused by aspiration o Hemorrhage, fibrin, necrosis o Complete resolution is uncommon
Histo
• Acute - massive fibrin + neutrophils in airspaces
• Chronic- Fibrosis of severely damaged tissues = permanent changes
Interstitial Pneumonia; histo, entry & two types of damage
Histo
• diffuse to patchy damage to alveolar septa
• Type II pneumocyte hyperplasia
Entry
o Aerogenous – inhalation of toxic gases
o Hematogenous – spread via the blood (most common)
Primary epithelial damage
o Toxic gasses, local generation of toxic compounds by metabolism in clara cells
o Damage secondary to viral infections
Primary endothelial damage
o Septicemia, DIC, migrating parasite larvae, endotheliotropic viruses, immune complex disease
Acute Bovine Pulmonary Edema & Emphysema (fog fever); pathogenesis, symptoms, histo
o Example of interstitial pneumonia
Pathogenesis
• Cow used to poor forage moved to lush pasture (high in L-tryptophan) ->
• L-tryptophan converted to 3-methylindole in rumen ->
• 3-MI absorbed into circulation ->
• Metabolized to toxic intermediate by Clara cells (toxic to pneumocytes and endothelium) ->
• Necrosis ->
• Acute edema and interstitial emphysema
Symptoms
• Severe dyspnea, froth from mouth, mouth breathing, extended neck
• NO FEVER
Histo
• Edema, emphysema, Type II pneumocyte hyperplasia
Chronic Interstitial Pneumonia; histo, gross lesions, causes
Histo Lesions
• alveolar fibrosis
• Macrophages, lymphocytes, plasma cells in interstitium
Gross Lesions
o Lungs don’t collapse
o rib impressions on surface of lungs
Causes
o Viral (mostly)
o Mycoplasma
Embolic Pneumonia
- Septic emboli lodge in lungs
- Bacteria trapped in vessels -> infections spreads into interstitium
- random multifocal distribution
Granulomatous Pneumonia; causes
- Well circumscribed, variably sized, firm nodules
- May be mineralized
- Random distribution
- Usually chronic
- aerogenous or hematogenous
Causes
o Fungi, bacteria, foreign material, migrating parasites
Neoplasia of the lungs
- Primary = uncommon
- Metastatic from other place common
- Ex: Feline lung-digit syndrome
Feline Lung Digit Syndrome
- primary pulmonary tumor (carcinoma or adenocarcinoma)
- commonly metastasize to digits
- mass on digits in cats indicative of pulmonary neoplasia
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Reserve Capacity of the kidney
- Can lose 66% of nephrons and have normal function
- loss of ~70% of nephrons = Isosthenuria
- loss of 70-75% of nephrons = Azotemia
- Further nephron loss = Renal Failure and Uremia
Function of the glomerulus
- Filtration barrier between blood and urinary space
* Restricts cells & proteins
Function of Proximal convoluted tubules
- Protein resorption (few that made it thru glomerulus)
- Resorption of 65% H2O, amino acids, glucose, Na, K, Cl
- High metabolism = sensitive to hypoxia & toxins
Function of Loop of Henle
- Resorption of 20% H2O, Na, Cl
* Maintains concentration gradient in medulla
Function of Distal Convoluted Tubule
- Resorption of water due to ADH
- Resorption of Na and excretion of K due to ALD
- Save the Na pee the potassium
Function of Collecting Duct
Resorption of H2O due to ADH
Blood Flow in the nephron
o nephrons required to maintain conc. gradient of interstitium
o conc. gradient in interstitium required for functional nephron
4 Nephron Endocrine Functions
Produces renin (RAS) o increases blood vol
Erythropoietin production
o In response to hypoxia
o Stimulates RBC production
Activates Vit D
o Helps Ca absorbtion
Degradation of PTH
o Ca homeostasis
How does renin increase blood volume?
o Decreased renal profusion (dehydration, hemorrhage, heart failure, etc) ->
o production of renin ->
o converts angiotensinogen into angiotensin I ->
o Ang I into Ang II by ACE produced by lungs ->
o Ang II vasoconstricts arterioles AND
o Ang II goes to pituitary to stimulate ADH production ->
o ADH causes resorption of water in distal tubules AND
o Ang II works on adrenal gland to produce ALD AND
o Ang II constricts efferent arterioles to insure time to filter blood
Azotemia
o Elevated BUN/creatinine
o Consequence of reduced GFR
Pre-renal
• Decreased renal profusion
• Azotemia but maintaining conc ability
Renal
• When >75% of nephrons are non-functional
• Azotemia w/ loss of ability to concentrate urine (isosthenuria)
Post Renal
• Obstruction of outflow of urine
Uremia
o Clinical syndrome due to renal failure
o Functional reserve of kidney lost
o Acute kidney injury or chronic renal failure
o Many multisystemic symptoms
Signs of Kidney Disfunction
- Azotemia
- Uremia
- change in urine quantity
- change in urine conc.
- Proteinuria
- Hematuria
- Glucosuria
- Urinary Casts
- Changes in production of erythropoietin, calcitrol, renin
Requirements to conc urine & chsnges in urine due to kidney dysfunction
Requirements to conc urine
• Functional interstitium
• ADH responsive epithelial cells in distal nephron
• ADH
o Polyuria
Isosthenuria: osmolarity of urine = plasma
• w/ Azotemia: likely renal failure
• No azotemia: may be appropriate or renal dz because conc. ability lost before azotemia shows
Proteinuria
Pre-renal
• Hemoglobinuria, myoglobinuria, bilirubinuria, ketonuria
Renal • Glomerular • increased permeability (very high) • Tubular • inability to resorb proteins (typically low)
Post Renal
• Most common
• Lower urogenital tract dz
Calcitrol & Renal Failure
o active Vit D3
o Produced via 1α-hydroxylase in renal tubular cells
o Promotes absorption of Ca from gut
o Chronic renal failure (CRF) can be associated with hypocalcemia
Erythropoietin & Renal Failure
o Produced by kidney in response to hypoxia
o Stimulates RBC production
o Chronic renal failure (CRF) can be associated with non-regenerative anemia
Renin & Renal Failure
o Chronic renal failure (CRF) -> increased renin ->
o Increased blood vol. ->
o Hypertension
Renal Dz Vs Renal Failure Vs End Stage Kidney
Renal Dz
o Lesions in kidney
Renal Failure
o Clinical syndrome due to decreased renal function
End stage
o Chronic, irreversible, progressive dz that results in common pathologic state
o Comparable to cirrhosis of liver
Kidney Response to Injury
o New nephrons not formed following renal maturation
o Nephron function is all or nothing
o Damage to one component = decreased function of other components
Glomerular Response to Injury
Acute
• Proliferation or necrosis of cells
• Rupture or thickening of basement membrane
• Infiltration of inflammatory cells
Chronic
• Atrophy and fibrosis of glomerular tuft
Tubule Response to Injury
- Epithelial cells: Degeneration, necrosis, atrophy
* Epithlium can regenerate if basement membrane is intact!
Interstitial Response to Injury
Acute:
• edema,
• hemorrhage,
• inflammation
Chronic:
• inflammation,
• fibrosis
Pre-renal disorders (Circulatory); USG, causes
Underperfusion
• Decreased GFR = azotemia w/ concentrated urine
• Activation of RAS
• If severe and prolonged -> Ischemic necrosis
Hyperemia / Congestion
• Acute septicemia
Hemorrhage
• Renal cortical or large
Infarction
• Vascular occlusion (wedge)
• Necrosis + hemorrhage -> fibrosis
Cortical necrosis
• DIC secondary to septicemia, endotoxemia
Medullary necrosis
• due to NSAIDs
How do NSAIDs cause medullary necrosis
- NSAIDs ->
- decreased prostaglandins ->
- vasoconstriction ->
- local ischemia ->
- necrosis
Pre-renal disorders (ADH disturbance)
o Diabetes insipidus
Neurogenic
• Pituitary gland does not produce ADH
• No ADH -> decreased urine concentration -> PU/PD
• Kidneys are normal
Nephrogenic
• ADH produced normally
• Kidney’s can’t respond -> decreased urine concentration
Pre-renal disorders (ALD disturbance)
Deficiency
• Adrenocortical insufficiency
• Excessive loss of Na & retention of K
• Elevated K -> bradycardia
Excess
• Excessive RAS activation
• congestive heart failure
4 Signs of Glomerular Dz
o Proteinuria
• Most important loss of Albumin
• Protein loss > resporptive capacity of PCT -> Proteinuria
• No azotemia & No change in GFR
o Hypoalbumenia
o Edema
• Decreased oncotic P -> activation of RAS -> fluid retention
o Hyperlipidemia
• Hypoalbuminemia -> increased synthesis of lipoproteins
Glomerular Nephritis basic & early stages Vs progressive
o “Inflammation” of the glomerular tuft
o common cause of renal failure in dogs
o usually cannot identify Ag involved
Early stages
• Urine concentrating ability is still intact
Progressive
• Loss of entire nephron -> renal failure/uremia/etc
Classification of Glomerular Nephritis
Membranous
• thickening of capillary basement membranes
Proliferative
• increased cellularity of glomerular tuft
Membranoproliferative
• Both
Pathogenesis of Glomerular Nephritis
- Endogenous or exogenous Ag Binds Ab ->
- Ag/ab complex circulates and lodges in glomerular capillaries ->
- Fix complement -> inflammation + bioactive mediators
Gross & Histological Lesions of Glomerular Nephritis
Gross Lesions • Often none! • Glomeruli may be prominent (red dots) • Chronic • Renal fibrosis = shrunken, granular, pale grey dots
Histo Lesions • Cellular proliferation • Thickening of the basement membrane • Abnormally porous • Glomerulosclerosis
Amyloidosis
o Less common than glomerular nephritis
o Amyloid may be deposited in other sites
o Mostly dogs, sometimes cows
o Present w/ CRF
o Always chronic, progressive and irreversible
o Breed dispositions: shar pei, Asian cats
Amyloidosis: Gross & Histological Lesions
Gross Lesions • Acute: o none • Chronic: o capsular surface irregular & mottled o iodine makes glomeruli black & prominent
Histology
• Amorphous eosinophilic material w/in glomeruli
• Congo red stain = apple green
• Advanced cases: extensive fibrosis
• Surviving tubules contain abundant protein casts
