Pathoma Ch 9, 12 (Resp Tract, Renal/Urinary Tract) Flashcards
-Resp Tract (ch9) -(ch19)
MC cause of
(a) rhinitis
(b) acute epiglottitis
(c) laryngotracheobronchitis
MC cause
(a) Rhinitis = adenovirus
(b) Acute epiglottitis = H. influenza B
- MC cause in BOTH vaccinated and unvaccinated
(c) laryngotracheobronchitis = croup = parainfluenza
What type of hypersensitivity is allergic rhinitis?
Type I hypersensitivity- preformed antibodies to pollen
List three causes of nasal polyps
- Recurrent rhinitis
- CF
- Aspirin-induced asthma
Triad of aspirin-induced asthma
Aspirin-induced asthma is seen in 10% of adult asthmatics
- Asthma
- Aspirin induced bronchospasm
- Nasal polyps
Demographic for angiofibroma of the nasopharynx
(a) Clinical presentation
Angiofibroma = benign tumor of BV, in young adult males
(a) Epistaxis
2 populations who you see nasopharyngeal carcinoma in
(a) Typical clinical feature
Nasopharyngeal carcinoma (associated w/ EBV) in African children and Chinese adults
(a) Cervical lymphadenopathy
Histologic findings of nasopharyngeal carcinoma
Key is keratin-positive cells- recall keratin is the intermediate filament of epithelial cells => keratin-positive proves its epithelium => carcinoma
Pleomorphic keratin-positive ep cells in background of lymphocytes
Explain physiology of vocal cord nodules
(a) Composition
(b) Clinical presentation
(c) Tx
Vocal cord nodules (‘nodesss!!! #pitchperfect) = nodule on the true vocal cords
(a) Myxoid (degenerative) CT from overuse
(b) Presents w/ hoarseness
(c) Voice rest
Laryngeal papilloma
(a) Etiology
(b) Adults vs. children
Laryngeal papilloma = finger-like projection on the larynx
(a) HPV serotypes 6 and 11 (low-risk)
- HPV => see koilocytic changes on histology
(b) Single in adults but multiple in children
2 RF for laryngeal carcinoma
Smoking and EtOH- same as for nasopharyngeal, basically squamous cell carcinomas due to exposure to smoking and EtOH in respiratory tracts
Explain how URI predisposes pt to superimposed bacterial pneumonia
(a) MC bacteria
Virus can impair the airway lining (cilia) => disrupt the mucociliary elevator used to clear stuff from airways
So decreased defenses => increased risk of bacterial superinfection
(a) Secondary pneumonia MC cause
1. strep pneumo (lobar)
2nd is staph aureus (bronchopneumonia)
2 main molecular mediators of pain
Bradykinin and PGE2 (prostaglandin E2)
MC cause of
(a) Lobar pneumonia
(b) Atypical pneumonia
(c) Pneumonia complicated by autoimmune hemolytic anemia
MC cause of
(a) Lobar pneumonia = strep pneumo
(b) Atypical pneumonia = mycoplasma pneumonia
(c) Mycoplasma pneumoniae can cause AI hemolytic anemia (IgM, cold agglutinin)
Which organism causes pneumonia w/ currant jelly colored sputum
Klebsiella pneumoniae- causes 5% of lobar pneumonias (other 95% are strep pneumo) has thick mucoid capsule causing gelatinous sputum (currant jelly)
GROSS
Bacterial pneumonia that is not visible on gram stain
Mycoplasma pneumoniae- not visible on gram stain due to lack of cell wall
MC cause of atypical (interstitial) pneumonia
Describe the pattern of pneumonia caused by H. influenzae and legionella pneumophila
Both H. influenzae and legionella pneumophila cause bronchopneumonia- scattered patchy consodliations centered around the bronchioles, often multifocal and b/l
Basically patchy and along the airways = bronchopnuemonia
Differentiate the pattern of involvement of bronchopneumonia and atypical pneumonia
Bronchopneumonia (S. aureus, H. influenza, pseudomonas, moraxella, and legionella) causes patchy infiltrates b/l along the airways
Interstitial/atypical pneumonia (mycoplasma, chlamydia, RSV, CMV, influenza, coxiella burnetii) causes infiltrate into the CT lining the alveoli (in the alveolar wall), so this causes increased pulmonary markings on CXR
MC bacteria involved in aspiration pneumonia
Anaerobic bacteria of the oropharynx
Bacteroides, Fusobacterium, Peptococcus
Name bacteria that you use silver stain to visualize
Bacteria mostly pseudomonas and legionella (both causes of bronchopneumonia)
Then also to stain fungi such as pneumocystis and candida
Name 2 organisms that commonly cause pneumonia superimposed on COPD
Pneumonia superimposed on COPD (leading to exacerbation of COPD) 2/2 H. influenzae and moraxella catarrhalis
Both of which cause bronchopneumonia (scattered patchy consolidations centered around bronchioles)
Young adult p/w interstitial pneumonia that is negative for mycoplasma
Next dx?
Chlamydia pneumoniae = 2nd MC cause of atypical pneumonia in young adults
MC cause of atypical pneumonia in
(a) young adults
(b) infants
(c) Posttransplant immunsuppressive therapy
MC cause of interstitial/atypical pneumonia in
(a) Young adults = mycoplasma
- 2nd is chlamydia pneumoniae
(b) Infants = RSV (respiratory syncytial virus)
(c) Posttransplant/immunosuppressed = CMV
What is Q-fever?
Q-fever = infxn caused by coxiella burnetti (rickettsial organism) that can cause interstitial (atypical) pneumonia
Presents w/ flu-like symptoms w/ high fever
Explain how elderly die if they die from the influenza virus
Influenza virus causes an atypical pneumonia in immunocompromised or existing disease, then this increases the risk of bacterial superinfection w/ S. aureus or H influenza
So they die from from the superimposed bacterial infection, not the influenza virus
MC organ involved when Tb spreads systemically
Kidneys, causing sterile pyuria
Sterile pyuria = elevated white count in urine w/o bacteria in urine
Ddx for caseating granulomas
- MTb (duh)
2. Fungi
Explain the physiology behind the clinical presentation of chronic bronchitis
Chronic bronchitis = productive cough for 3+ months over at least 2 years due to hypertrophy of the bronchial mucinous glands
-basically the mucous glands (produce mucus) hypertrophy in response to cig smoke => tons of mucus secreted
‘blue bloaters’ vs. ‘pink-puffers’
Two types of obstructive pulmonary disease
Blue-bloaters = chronic bronchitis- cyanosis b/c mucus plugs trap CO2
Pink-puffers = Emphysema- prolonged expiration w/ pursed lips, increased work of breathing
Explain the cause of obstruction in emphysema
In emphysema the obstruction is not physical as seen by mucus plugs in chronic bronchitis
Instead the loss of recoil of the interstitium decreases force at which air is pushed out, also loss of recoil of the non-cartilage containing bronchioles causes collapse of airways (air stuck behind collapsed airways)
Explain how alveolar air sacs are destroyed in emphysema
Emphysema: imbalance btwn proteases (elastase and other proteases from neutrophils called in by inflammation) and anti-proteases from chronic inflammation
Aka cig smoke increases inflammation => more neutrophils produce more proteases that overwhelm the antiproteases
Explain why the risk of cirrhosis is increased in alpha-1 antitrypsin
B/c misfolded alpha-1 antitrypsin protein accumulates in the endoplasmic reticulum of the hepatocytes
Differentiate clinical features of chronic bronchitis and emphysema
Chronic bronchitis- very productive (literally buckets of sputum) cough, cyanosis (blue bloaters)
Emphysema- non-productive cough, prolonged expiration w/ pursed lips (auto-PEEP)
Both have increased risk of hypoxemia and cor pulmonale
What is the FRC?
(a) How is it changed in emphysema?
(b) Change seen in pulmonary fibrosis?
FRC = functional reserve capacity = where the curves meet btwn chest wall pulling outwards and pulmonary recoil pulling inwards
(a) In emphysema the recoil is decreased => FRC increases
- see ‘barrel chest’/increased AP diameter on CXR
(b) Pulmonary fibrosis- FRC decreased b/c fibrosis keeps lung stiff and inwards
Explain development of core pulmonale 2/2 obstructive lung disease
Lungs vasoconstrict perfusion to areas of low ventilation, but doesn’t know that there are no good areas on ventilation in diffuse obstructive disease => diffuse vasoconstriction of pulmonary vasculature makes high resistance for right heart to push against
What type of hypersensitivity is asthma?
(a) Main cell type involved in initial exposure?
Asthma = type I hypersensitivity, pre-sensitized IgE release histamine immediately in response to exposure
(a) Initial exposure- Th2 phenotype CD4 T cells are the main cells involved
Give the function of the the three main interleukins released in asthma response
Th2 type CD4 cells secrete
- IL-4: mediates class switch of plasma cell to IgE
- IL-5: attracts eosinophils
- IL-10: stimulates Th2 cells and inhibits Th1 cells, so propagates more Th2
Differentiate the factors that mediate the early phase and late phase reactions in asthma
Reexposure to allergic leads to IgE-mediated activation of mast cells
Early phase reaction = release of preformed histamine granules (vasodilation of arterioles, venule leakiness) and leukotriene release
Then late-phase reaction maintained by major basic protein from eosinophils to perpetuate the bronchoconstriction
Name some nonallergic causes of asthma
- exercise
- infection
- aspirin (seen w/ bronchospasm and nasal polyps
- occupational exposures
What is bronchiectasis?
(a) Obstructive or restrictive?
Bronchiectasis = permanent dilation of bronchioles and bronchi (distal airways)
(a) Obstructive b/c dilation causes loss of airway tone resulting in air trapping, can’t generate enough velocity to get air of larger tubes
Defect that causes Kartagener syndrome
Inherited defect of the dynein arm of cilia => primary ciliary dysmotility
-sinusitis, infertility, situs inversus
Name an infectious cause of bronchiectasis
ABPA = allergic bronchopulmonary aspergillosis = hypersensitivity rxn to Aspergillus that causes chronic inflammatory damage
Which subtype of obstructive pulmonary disease can cause foul-smelling sputum?
Bronchiectasis- dilated airways get build up behind them => mucus stays trapped (ew gross)
-CF pts, Kartagener’s
Pathophysiology of idiopathic pulmonary fibrosis
IPF: fibrosis (thickening) of the intersititum of the lungs (wall of alveoli)
-cyclic lung injury (from unknown cause, hence idiopathic) causes release of TGF-beta from injured pneumocytes, its this TGF-beta that induces fibrosis
Key here is TGF-beta => fibrosis
2 drugs classically implicated in secondary pulmonary fibrosis
- bleomycin
2. amiodarone
Tx for idiopathic pulmonary fibrosis
Lung transplant b/c can’t remove the fibrosis, can’t thin the alveolar walls!
Explain the physiology of pneumoconioses
Pneumoconioses = interstitial pulmonary fibrosis due to chronic environmental exposure (MC occupational) to small particles (have to be small so can get to the most distal airways) that are fibrogenic (have to stimulate alveolar macrophages to induce fibrosis)
Differentiate anthracosis and coal workers’ pneumoconiosis
Anthracosis = clinically benign mild exposure to carbon that causes collection of carbon-laden macrophages
-super common 2/2 air pollution
Far extreme form = chronic exposure to carbon dust seen in coal miners => diffuse fibrosis (‘black lung’)
-lolllllz “Paaaa I think I caught the black lung” #zoolander
Which pneumoconiosis increases the risk for TB infection
Silicosis (silica exposure, sandblasts and silica miners) impairs phagolysosome formation => increases risk of TB
Which pneumoconiosis pathologically looks like sarcoidosis?
Berylliosis (beryllium exposure in aerospace injury) causes noncaseating granulomas in lungs, hilar LN, and systemic organs (same pathology as sarcoid!)
So if question is a NASA worker than seems to have sarcoid, think about berylliosis
MC cancer 2/2 asbestosis exposure
WATCH OUT
MC is still lung carcinoma
There is an increased risk of mesothelioma, but STILL THE MC is lung carcinoma
Sarcoidosis
(a) Obstructive or restrictive lung disease?
(b) MC presenting symptom
(c) Classic demographic
Sarcoidosis
(a) Restrictive- granulomas restrict filling b/c reduce compliance of interstitium
(b) Cough
(c) African American females
2 lab value abnormalities in sarcoidosis
Sarcoidosis
- elevated ACE
- Hypercalcemia- epithelioid histiocytes contain active 1-alpha hydroxylase that activates vitamin D
- seen in any disease w/ noncaseating granulomas (ex: Berylliosis too from beryllium exposure)
Name tissues besides lung that are commonly involved in Sarcoidosis
Uvea- uveitis
Skin- cutaneous nodules or erythema nodosum
Salivary/lacrimal glands- can mimic Sjogrens
-but almost any tissue can be involved
MC location of granulomas in sarcoidosis
Noncaseating granulomas in multiple organs, but MC involving hilar lymph nodes and then lung
Granulomas w/ eosinophils
(a) Dx
(b) Long term consequence
Granulomas w/ eosinophils (a) Hypersensitivty pneumonitis (pigeon breeder from Hey Arnold)
(b) Interstitial fibrosis after long term exposure to antigen (pigeon poop)
Mutation associated w/ primary pulmonary hypertension
Young adult females w/ inactivating mutations of BMPR2 leading to proliferation of vascular smooth muscle which thickens the pulmonary vessel walls
Define pulmonary hypertension
(a) Locate the atherosclerosis
High pressure in pulmonary circuit, defined as over 25 mmHg (while normal is 10 mmHg)
(a) Atherosclerosis of the pulmonary artery
Why does ARDS recover w/ interstitial fibrosis and not just regeneration as seen in mild pneumonias
ARDS- free radicals damage the type I and type II pneumocytes (stem cells)
When stem cells are damaged you can’t regenerate the tissue => regenerates w/ fibrosis and scar
2 functions of type II pneumocytes
Type II pneumocytes produce surfactant and are the stem cells to regenerate type I
Why may maternal diabetes increase risk of neonatal respiratory distress syndrome
Maternal insulin doesn’t cross placenta but maternal glucose crosses placenta and causes fetus to overproduce insulin, then fetal insulin inhibits surfactant production
How does neonatal respiratory distress syndrome increase risk of
(a) PDA
(b) necrotizing enterocolitis
(c) blindness
NRDS
(a) Patent ductus b/c not the right oxygen tension to close
(b) Nec b/c less O2 to the gut
(c) Blindness b/c ROS damage to the eye
- before we gave steroids to increase fetal surfactant production, NRDS was one of the leading causes of neonatal blindness
Main carcinogen found in cig smoke
Polycyclic aromatic hydrocarbons
2 causes of benign ‘coil lesions’ found on CXR
Coin lesions (esp in young pts) can be benign
- Granuloma- Tb or fungus (ex: histoplasma in midwest)
- Bronchial hamartoma = benign tumor of lung tissue and cartilage
Small cell vs. non-small cell lung carcinoma
(a) MC
(b) Tx
Lung carcinoma divided into two categories
Small cell
(a) 15%
(b) ‘cells to small for surgeon to get’- tx primary w/ chemo/radiation, usually not amenable to surgical resection
Non-small cell
(a) 85% so much more common and hads bunch of subtypes: adenocarcinoma, squamous cell, large cell, carcinoid
(b) first line tx is surgical resection
Which lung cancers are
(a) Central
(b) Peripheral
Lung cancer
(a) “Sentral” for squamous cell and small cell
(b) Peripheral- adenocarcinoma
Two type of lung cancers that stain chromogranin positive
Both small cell carcinoma (poorly differentiated from neuroendocrine cells) and carcinoid tumor (well differentiate neuroendocrine cells in nests) stain chromogranin positive
Clinical presentation of SVC syndrome
SVC obstruction (ex: from lung cancer) causes distended head and neck veins w/ edema, blue discoloration of arms and face (can’t drain venous blood out)
Unique place that lung cancer likes to met to
Adrenal glands
Clinical presentation of mesothelioma
Recurrent pleural effusions (b/c mesothelial cells normally secrete fluid to keep the pleural space lubricated), dyspnea, chest pain
MC lung cancer in
(a) Nonsmokers
(b) Male smokers
(c) Female smokers
MC lung cancer in
(a) Nonsmokers = adenocarcinoma
(b) Male smokers = squamous cell carcinoma
(c) Female smokers = adenocarcinoma
Histologic finding of large cell carcinoma of the lungs
Poorly differentiated large cells
- no keratin pearls or intracellular bridges (seen in squamous cell carcinoma)
- no glands or mucin (as seen in adenocarcinoma)
MC congenital renal anomaly
MC congenital renal anomaly = horseshoe kidney
-fused at lower poles
Clinical presentation of unilateral renal agenesis
Unilateral renal agenesis asymptomatic at birth- causes hypertrophy of the other kidney, then over time hyperfiltration of the single kidney increases risk of renal failure later in life
Clinical presentation of b/l renal agenesis
B/l renal agenesis = no urine = oligohydramnios => Potter sequence
- pulmonary hypoplasia (b/c lungs need fluid to stretch them for proper development)
- flat facies w/ low set ears and limb/extremity defects (b/c w/o fluid to float in these things get smushed against maternal structures)
Potter sequence
B/l renal agenesis or b/l renal defect = no urine = oligohydramnios => Potter sequence
- pulmonary hypoplasia (b/c lungs need fluid to stretch them for proper development)
- flat facies w/ low set ears and limb/extremity defects (b/c w/o fluid to float in these things get smushed against maternal structures)
Name a noninherited caused of cystic kidney disease
(a) How to differentiate from PKD
Noninherited cystic kidney disease = Multicystic Dysplastic kidney, noninherited but congenital malformation of the renal parenchyma
-cysts and abnormal tissue (often cartilage)
(a) PKD is more commonly b/l (but dysplastic kidney can be b/l MC unilateral). presence of abnormal tissue in dysplastic kidney
Differentiate the mode of inheritance of the two forms of polycystic kidney disease
(a) Presents in infants
(b) Presents in young adults
PKD
(a) Aut recessive form presents in infants w/ worsening renal failure and HTN
(b) Aut dom form (APKD1 or APKD2 mutation) presents in young adults w/ HTN, hematuria, and worsening renal failure
- b/c cysts develop over time (not present at birth)
Autosomal recessive polycystic kidney disease
(a) Age of presentation
(b) 2 associated conditions
Aut recessive PKD
(a) Presents in infants w/ worsening renal failure and HTN b/c the cysts are present at birth
(b) ‘Cysts in kidney and liver’- associated hepatic cysts and congenital hepatic fibrosis that leads to portal HTN
Autosomal dominant polycystic kidney disease
(a) Age of presentation
(b) Associated conditions
Aut dom PKD 2/2 mutation in APKD1 or APKD2
(a) Presents in young adults b/c cysts aren’t present at birth, develop over time, then present w/ HTN, hematuria, and worsening renal failure
(b) ‘Cysts in kidney, liver, and brain’- associated hepatic cysts and berry aneurysm (cystic dilation of intracranial arteries)
- also associated mitral valve prolapse
How to differentiate polycystic kidney disease from medullary cystic kidney disease
Both are inherited cystic kidney diseases
Medullary kidney disease- cysts only develop in the medullary collecting ducts, vs. in both medulla and cortex of PKD
Medullary cystic disease- parenchymal fibrosis leads to shrunken kidneys, vs. enlarged b/l kidneys in PKD
Explain the BUN:Cr ratio seen in prerenal azotemia
Both BUN and Cr are normally filtered, but Cr doesn’t really get reabsorbed (most excreted in urine) while BUN gets actively resorbed
So when tubules are functioning properly, BUN:Cr ratio is about 15:1
Then in prerenal azotemia (low flow), renin released –> high aldo so reabsorb more water and BUN follows so BUN:Cr > 15, indicating tubules are functioning properly
FENa seen in
(a) Prerenal azotemia
(b) Early postrenal azotemia
(c) ATN
FENa (fractional excretion of Na)
(a,b) Tubules are functioning properly so FENa is under 1%
(c) Tubules are damaged => can’t properly reabsorb Na => FENa over 2%
Give an etiology of
(a) Prerenal azotemia
(b) Postrenal azotemia
Etiology
(a) Prerenal azotema- low flow state (hypovolemia), dehydration, low cardiac output (heart failure)
(b) Postrenal azotemia- ureteral obstruction, bladder outlet obstruction
Urine osmolality in
(a) Prerenal azotemia
(b) Early postrenal azotemia
(c) ATN
Urine osmolality
(a,b) Tubules working properly to concentrate urine so Uosms over 500
(c) ATN tubules are damaged and can’t properly concentrate urine, Uosm under 500
Differentiate the findings in early vs. long-standing postrenal azotemia
Postrenal azotemia- in the beginning tubules are functioning properly so FENa under 1% and Uosm over 500, then over time from obstruction pressure the tubules get damaged => see FENa rise and Uosm decrease (b/c tubules can no longer function to concentrate urine)
MC cause of acute intrarenal azotemia
MC cause of intrarenal azotemia = acute tubular necrosis (more common than acute interstitial nephritis)
Explain the physiology of ATN
(a) BUN:Cr ratio
(b) FENa
ATN: injury and necrosis of the tubular epithelial cells causes necrotic cells to plug the tubules, this obstruction decreases GFR
(a) BUN:Cr ratio under 15 b/c tubules not functioning so can’t resorb BUN
(c) FENa over 2% b/c decreased Na reabsorption
Which part of the nephron is most susceptible to ischemic vs. nephrotoxic causes of ATN
Proximal tubule and medullary segment of thick ascending limb are most susceptible to toxic damage b/c highest O2 (ATP) requirement
Proximal tubule gets hit first by the toxin => most susceptible to nephrotoxic agents
MC toxic agent responsible for ATN
MC toxic agent = aminoglycosides (Streptomycin, Gentamycin, Tobramycin, Amikacin)
Type of AKI caused by radiocontrast dye
Radioconstrast dye is a toxin that causes necrosis of the tubules => nephrotoxic ATN
How to reduce the risk of urinate induced ATN 2/2 chemotherapy administration
Tumor lysis syndrome can release tons of urate that is toxic to the nephron => administer chemo with tons of fluid and allopurinol (inhibit urate production) to reduce risk of ATN w/ chemo
Ethylene glycol (antifreeze) causes what kind of AKI?
(a) What kind of urine crystals?
Ethylene glycol => nephrotoxic ATN
(a) Oxalate crystlas
Metabolic abnormalities caused by ATN
ATN => hyperkalemia and anion-gap metabolic acidosis 2/2 reduced excretion of K+ and H+
How long does ATN vs. AIN last?
Oliguria in ATN can last 2-3 weeks b/c tubular cells are stable cells- means they can re-enter the cell cycle but they’re not actively dividing, so takes a bit of time for tubular cells to reenter the cell cycle and regenerate
AIN is a hypersensitivity rxn => resolves immediately w/ cessation of the drug
What type of reaction is AIN?
(a) 3 main causes
AIN = drug-induced hypersensitivity rxn involving interstitium and tubules
(a) NSAIDs, penicillins, diuretics
Clinical presentation of AIN
(a) Main lab finding
(b) Most feared complication
AIN presents as oliguria, fever, and rash days to weeks after starting a drug
(a) Eosinophils may be seen in urine
(b) Renal papillary necrosis = necrosis of renal papillae
Name some causes of papillary necrosis
Necrosis of the renal papillae presents w/ gross hematuria and flank pain, can be from recurrent AIN drug-induced hypersensitivity rxns
Causes:
-chronic analgesic (ex: ASA) use
Young adult p/w hematuria
-father w/ died of intracranial hemorrhage
Dx?
Autosomal condition w/ renal cysts and berry aneurysms = aut dom polycystic kidney disease
Presents in young adults w/ worsening renal failure, HTN, hematuria b/c cysts need time to develop (not present at birth like in aut recessive PKD), associated hepatic cysts, berry aneurysms, and mitral valve prolapse
Brown muddy casts
UA finding of acute tubular necrosis
Brown muddy casts
UA finding of acute tubular necrosis
MC cause of
(a) Nephritic
(b) Nephrotic
syndrome in lupus pts
SLE pts
(a) Nephritic syndrome = diffuse proliferative glomerulonephritis- granular (immune complex) IF = IC are subendothelial
(b) Nephrotic syndrome = membranous nephropathy = IC are subepithelial
Clinical manifestations of nephrotic syndrome
Nephrotic syndrome: proteinuria of over 3.5 g/day
- hypoalbuminemia => pitting edema (2/2 loss of interstitial oncotic pressure)
- hypogammaglobulinemia => increased risk of infection
- pee out tons of ATIII => hypercoagulable state
- hyperlipidema and hypercholesterol b/c liver realized blood is ‘thin’ (low proteins) so pumps out thickeners
Nephrotic vs. nephritic syndrome
(a) Amount of protein in urine
(b) Casts found in urine
Nephrotic
(a) over 3.5 g/day of proteinuria
(b) Not usually, but can see fatty casts in urine 2/2 dyslipidemia b/c liver pumps out lipids 2/2 thin blood (low protein)
Nephritic
(a) Under 3.5 g/day
(b) See RBC casts (sign of glomerular bleeding) and dysmorphic RBCs in the urine b/c characterized by glomerular inflammation and bleeding
Minimal change disease is associated w/ what malignancy?
MCD is associated w/ Hodgkin lymphoma
Podocyte damage in MCD is 2/2 cytokine release, and Reed-Sternberg cells in HL release TONS of cytokines
MC cause of nephrotic syndrome in
(a) Hispanics and African Americans
(b) Caucasians
(c) MC nephropathy worldwide
Nephrotic syndrome in
(a) Hispanics and African Americans = Focal segmental glomerulosclerosis- no immune complexes, get focal and segmental sclerosis of glomerulus
(b) Caucasians = Membranous Nephropathy where immune complexes deposit subepithelialy
(c) MC nephropathy worldwide = IgA nephropathy (nephritic)
Nephrotic syndrome associated w/
(a) HBV and HCV
(b) SLE
(c) HIV, heroin use
(d) SCD
Nephrotic syndrome associated w/
(a) Hep B and C = type I membranoproliferative glomerulonephritis (MPGN)
-type I has subendothelial deposits
(b) SLE more commonly nephritic syndrome, but if nephrotic = membranous nephropathy
(c,d) HIV, heroin use, and SCD associated w/ FSGS (focal segmental glomeruloscerlsosi
Tx of nephrotic syndrome as a whole
All except MCD are minimally responsive to steroids
- So FSGS, membraneous nephropathy, MPGN have poor response to steroids
- for diabetes give ACEi to slow down hyperfiltration damage
Dx to suspect when young adult w/ podocyte effacement on EM does not respond to steroid tx
Podocyte effacement Ddx = MCD and FSGS
but MCD mroe common in children and has excellent response to steroids, so if non-responsive to steroids think more FSGS
Nephrotic syndrome w/
(a) Spike and dome appearance on EM
(b) Tram track appearance
Nephritic syndrome w/
(a) Spike and dome appearance = membranous nephropathy
- due to immune complex deposition subepithelially, podocytes lay more basement membrane which domes over the immune complex
(b) Tram track appearance of MPGN b/c proliferation of mesangial cell cuts the immune complex in half like a tram track
Which nephrotic syndrome is associated w/ C3 nephritic factor?
C3 nephritic factor = autoantibody that stabilizes C3 convertase => overactivation of complement b/c usually C3 convertase makes C3a and C3b rather quickly so that C3 doesn’t remain active
Overactivation of complement => inflammation and low circulating C3 seen in type II membranoproliferative glomerulonephritis
First pathological step in diabetic nephropathy
Nonenzymatic glycosylation of the vascular basement membrane
Describe the mechanism of diabetic nephropathy
(a) What causes microalbuminemia?
Nonenzymatic glycosylation of the basement membrane causing hyaline arteriolosclerosis
(a) Preferential hyaline arteriolosclerosis (thickening) of efferent arteriole increases the glomerular filtration pressure which causes hyperfiltration
Hyperfiltration injury => microalbuminuria that eventually progresses to nephrotic syndrome
Mechanism by which ACEi decreases risk of diabetic nephropathy
In diabetic nephropathy there is preferential hyaline arteriolosclerosis of the efferent arteriole which increases filtration pressure, eventually damaging glomerulus => nephrotic syndrome
ATII preferentially vasoconstricts efferent arteriole- so worsens this filtration pressure => ACEi slows progression of hyperfiltration-induced glomerular damage
Explain the mechanism by immune complex damage causes inflammation seen in nephrotic syndrome
Immune complexes deposit which activates complement, then C5a goes on to activate neutrophils which mediate inflammatory damage
Which strains of streptococcus can cause nephritic syndrome
Group A strep strains that are nephritogenic are the ones that carry M-protein virulence factor
W/o M-protein the strain can’t cause PSGN
-usually strains that cause impetigo and strep pharyngitis have M-protein
Poor prognostic factor for post-strep GN
Older age! Only 1% of children progress to renal failure, while almost 25% of adults develop rapid progressive glomerulonephritis
What is rapid progressive glomerulonephritis?
(a) Timeline to renal failure
(b) Nephrotic or nephritic?
(c) Typical H&E finding
(d) How to determine etiology
RPGN
(a) Rapid as in weeks to months until progresses to renal failure
(b) Nephritic syndrome- inflammation and bleeding of the glomerulus
(c) Crescentic formation in glomerulus
(d) Determine etiology by immunofluorescence (see if and where immune complexes are)
MC type of renal disease in SLE
MC renal disease in SLE = diffuse proliferative glomerulonephritis which is a subtype of rapidly progressive glomerulonephritis (nephritic syndrome)
Name the dx when IF of rapidly progressive glomerulonephritis shows
(a) No ICs
(b) Linear pattern
(c) Granular pattern
Immunofloresence
(a) No immune complexes = pauci-immune = vasculitis etiology: Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome
(b) Linear pattern = anti-basement Ab seen in Goodpasture syndrome
(c) Granular pattern = IC deposition seen in post-strep Gn and diffuse proliferative glomerulonephritis
Differentiate the 3 pauci-immune etiologies of rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis (nephritic syndrome w/ crescentic pattern that progresses to renal failure w/in weeks to months) that doesn’t have immune complex deposition on immunofluorescence = pauci-immune
c-ANCA = Wegeners granulomatsosi
p-ANCA = Microscopic polyangiitis and Churg-Strauss
Clinical presentation of IgA Nephropathy
IgA nephropathy presents w/ episodic microscopic hematuria (RBC casts) following mucosal infection
Mucosal infection increases IgA production => more IgA immune complexes deposit in mesangium of glomerulus => RBC casts in urine
Inheritable cause of nephritic syndrome
Alport syndrome = X-linked defect in collagen IV causing nephritic syndrome w/ hearing and visual difficulties
Mechanism of poststreptococcal glomerulonephritis
Immune complex deposition subepithelially secondary to M-protein virulence factor of Group A strep
How to differentiate p-ANCA pauci-immune rapidly progressive glomerulonephritis
Two p-ANCA positive causes of RPGN = Microscopic polyangiitis and Churg-Strauss
Churg-Strauss will have granulomatous inflammation, eosinophilia, and asthma (differentiating factors)
Clinical features of cystitis vs. pyelonephritis
Cystitis- urinary frequency and dysuria (pain w/ urination) but w/o the systemic features (fever) seen w/ pyelo
Cystitis
(a) UA finding
(b) Dipstick
(c) Cx gold standard
Cystitis
(a) UA finding: over 10 WBC per high power field
(b) Dipstick positive for nitrates (made by bacteria) and leukocyte esterase
(c) Cx w/ over 100k colonies = gold standard
Name 4 organisms responsible for cystitis in addition to E. Coli
Cystitis
80% E. Coli Staph saprophyticus Klebsiella Proteus mirabilis Enterococcus faecalis
Which organism causes cystitis w/ alkaline urine and ammonia scent
Proteus mirabilis => alkaine urine w/ ammonia scent
What lab findings suggest urethritis over cystitis?
(a) Organisms responsible
Sterile pyruria = over 10 WBC/hpf and positive leuk esterase but w/ negative urine culture
(a) Urethritis think neisseria gonorrhea and chlamydia trachomatis
3 MC causes of Pyelonephritis
Pyelo
90% E. coli
Enterococcus faecalis
Klebsiella
2 causes of chronic pyelonephritis
(a) What type of casts seen in urine
Chronic pyelo 2/2 VUR or obstruction (BPH, cervical carcinoma)
(a) Waxy casts on UA indicative of chronic pyelo
What causes ‘thyroidization’ of the kidney
Chronic pyelonephritis- atrophic tubules contain eosinophilic proteinaceous material that resembles colloid seen in thyroid follicles
Tx of the MC type of nephrolithilasis
MC kidney stone = calcium oxalate and/or calcium phosphate
Tx by decreasing calcium in urine w/ HCTZ = Ca2+ sparing diuretic
2nd MC type of kidney stone
(a) Cause
(b) Why does tx involve surgery
2nd MC kidney stone = ammonium magnesium phosphate stone
(a) MC caused by urease-positive organism infection (proteus vulgaris or Klebsiella) b/c the alkaline urine leads to formation of stone
(b) B/c classically causes a staghorn calculi in the renal calyce which acts as a nidus for UTI => need to remove the huge stone then also tx w/ abx
Which types of kidney stones are visible on imaging?
2 MC types (calcium oxalate/phosphate and ammonium magnesium phosphate) stones are radiopaque = visible on Xray
While uric acid stones (about 5% of kidney stones) are radiolucent = won’t show up on Xray
RF for uric acid kidney stones
Hot arid climates, low urine volume (b/c low volume means high concentration of solute), acidic pH, hyperuricemia (leukemia, myeloproliferative d/o, gout)
Tx for uric acid kidney stones
Hydration and alkalinization of urine (w/ potassium bicarbonate)
-b/c acidic pH increases uric acid precipitation
Allopurinol if pt has gout
Type of kidney stone more commonly seen in children than adults
Cystine kidney stone MC in children than adults b/c of cystinuria = genetic defect in tubules from decreased ability to reabsorb of cysteine
Explain these clinical features of chronic renal failure
(a) HTN
(b) pH abnormality
(c) Hypercoagulability
Chronic renal failure
(a) HTN b/c of salt and water retention
(b) Hyperkalmeia w/ metabolic acidosis (not excreting H+ out collecting duct)
(c) Hypercoagulability b/c uremia causes plt dysfunction
Explain these clinical features of chronic renal failure
(a) Anemia
(b) Hypocalcemia
(c) Osteitis fibrosa
Chronic renal failure
(a) Anemia 2/2 lack of EPO production by renal peritubular interstitial cells
What cancer does dialysis increase risk for?
Renal cell carcinoma
Renal neoplasm associated w/ tuberous sclerosis
Angiomyolipoma = hamartoma of BV (angio), smooth muscle (myo), and fat (lipo)
Renal cell carcinoma
(a) Cell of origin
(b) MC clinical symptom
(c) Right or left vericocele
RCC
(a) Malignant epithelial tumor of tubular cells
(b) Hematura = MC symptom, classic triad hematuria palpable mass and flank pain only present all 3 10% of the time
(c) Left vericocele b/c RCC likes to spread to the renal vein, L renal vein involvement blocks drainage of left renal vein
Name the paraneoplastic syndromes that can be seen 2/2 RCC
Renal cell carcinoma can produce EPO, renin, PTHrP, or ACTH
-so polycythemia, HTN, hypercalcemia, Cushings
Gene mutation seen in RCC
Pathogenesis of RCC = loss of VHL tumor suppressor gene => increased IGF-1 that promotes growth
Major RF for sporadic renal cell carcinoma
(a) Location of sporadic form
Smoking = major RF
(a) Sporadic form typically in males over 60, arises as single tumor in upper pole
Differentiate sporadic from hereditary renal cell carcinoma
Hereditary tumors arise in younger adults, not associated w/ smoking, and are often bilateral
ex: VHL disease = aut dom inactivation of VHL gene
Unique feature of T-staging for renal cell carcinoma
Size of tumor but also includes involvement of the renal vein (very common)
Composition of Wilms tumor
(a) Average age
Wilms tumor = malignant tumor comprised of blastema = immature kidney mesenchyme that forms primitive glomeruli, tubules,and stromal cells
(a) 3 yoa
Renal cell carcinoma MC subtype
(a) Gross pathologic feature
(b) Histologic appearance
RCC MC subtype = clear cell
(a) Grossly yellow mass
(b) MC subtype shows clear cytoplasm
Clinical presentation of Wilms tumor
Wilms tumor = malignant kidney tumor of blastema presents as large unilateral flank mass (lateral, not central) p/w hematuria and hypertension (HTN 2/2 renin secretion)
Long term cyclophosphamide increases risk of what cancer?
Long term cyclophosphamide increases risk of urothelial (transitional) cell cancer- MC of the bladder
Urothelial carcinoma
(a) MC location
(b) Why often multifocal
Urothelial carcinoma = transitional cell carcinoma of the lower urinary tract
(a) MC bladder
(b) Field defect b/c the carcinogen hits the entire urothelium => tumors often multifocal and recur
What is a necessary precursor lesion to squamous cell carcinoma of the bladder?
Bladder is transitional epithelium, therefore squamous metaplasaia must occur before SCC can arise
Squamous cell metaplasia from chronic irritation of the urothelium
ex: from chronic cystitis, Schistosoma haematobium infection (Egyptian, middle eastern male), long-standing nephrolithiasis
Embryological defect that increases risk of bladder adenocarcinoma
Urachal remnant (urachus drains waste from fetal bladder into yolk sac) can form adnocarcinoma of the bladder- tumor develops at the dome of the bladder
