Volume Disorders
Causes Sx/Characteristics
Pseudohyponatremia or Hyperglycemia Increase in total plasma solids Normal serum osmolality
(high TG or high total protein)
Hypotonic States Primary Polydipsia Psychogenic H₂O consumption greater Psychogenic: Osm 200
Volume-expanded state from primary renal
H₂O retention
Glucocorticoid deficiency → increased ADH secretion Normal EAV, urine Osm > 200
Hypothyroidism → increased ADH secretion Normal EAV, urine Osm > 200
Myxedema?
Drugs chlorpropamide, carbamazepine, Normal EAV, urine Osm > 200
vincristine, cyclophosphamide,
antipsychotics
Renal failure Normal EAV, urine Osm > 200
Edematous disorders CHF Low EAV, urine Osm > 200, normal EFV
cirrhosis
nephrosis
Severe volume depletion Low EAV, urine Osm > 200, low EFV
Hypertonicity Hypovolemic w/ GI tract H₂O loss Diarrhea, vomiting
(high plasma accelerated H₂O loss Skin H₂O loss Burns, fever
[Na]) Kidney - osmotic diuresis Loss of non-Na solutes like glucose, urea, Polyurea, polydipsia
mannitol Concentrated urine
Relief of acute obstruction
Diuretics
Euvolemic w/ pure Kidney - central diabetes insipidus ADH secretion from PP inhibited Polyurea, polydipsia
H₂O loss (trauma, tumors, granulomas, infection, Doesn't respond to H₂O deprivation
familial) Responds to ADH
Kidney - nephrogenic diabetes insipidus "Resistance" to ADH secretion Polyurea, polydipsia
(urinary obstruction, hypokalemia, Doesn't respond to deprivation or ADH
hypercalcemia, amyloidosis, sickle cell,
polycystic kidney dz, drugs [Li, Tx is thiazide (slows free H₂O flow)
demeclocycline, methoxyflurane], familial
X-linked disorder)
Hypervolemic Hypertonic NaHCO3 administration
Hypertonic feedings
K Disorders
Causes Sx/Characteristics Notes
Hypokalemia Intake Consuming too little K Unusual
Kidney can lower
GI Diarrhea Urinary K 20
(high BP, low renin, high aldo) Low renin, high aldo mEq/L
Glucocorticoid suppressible Autosomal dominant Hypokalemia variably present No hx of
hyperaldosteronism Chimeric gene formed by crossover of ACTH diarrhea/laxitives
response to aldo coding region
↑ aldo secretion by zona fasciculata All couple distal sodium
Primary hyperreninism Malignant hypertension High renin, High aldo HypoK in 50% delivery to high
(high BP, high renin, high aldo) Renal artery stenosis High renin, High aldo HypoK in 15% aldosterone excess
High BP, EABV
Renin secreting tumor High BP, EABV 1⁰ causes of high distal
High renin, High aldo sodium delivery:
Increased non-aldo mineralocorticoid Cushing's syndrome Low renin, low aldo Diuretics
(high BP, low renin, low aldo) Hypertension Mg deficiency
CAH (11βhydroxy or 17αhydroxy deficiency) Virilization Bartter syndrome
↓ sex hormones Gittelman's
Genetic Hypokalemia & hypertension Liddle syndrome Low renin, low aldo Increased ENaC channel activity Nonreabsorbed anions
(high BP, low renin, low aldo) Hypertension (gain of function mutation)
No response to aldo inhibitor, spironolactone (mutation to constitutive activity)
Tx: triamterene, transplant
No response to spironolactone
Syndrome of apparent mineralocorticoid Looks like Cushing's Glyceratinic acid poisoning from
excess licorice
(11β-OSHDH-2 inhibition) Enzyme usually blocks cortisol
targeting of mineralocorticoid receptor
(→ cortisone)
Distal Na delivery w/o high BP, EABV RTA Low serum HCO3
(low BP) Metabolic alkalosis Vomiting
NRA (Non-reabsorbed anions) High serum HCO3, low urine [Cl] HCO3, ketoanions, penicillins,
hippurate, salicylate
Diuretics, Mg def, Bartter, Gittelman High serum HCO3, high urine [Cl]
Cellular Alkalosis Trivial effects
redist. Insulin/↑ β adrenergic activity
Hypokalemic periodic paralysis Acquired: thyrotoxicosis in Asians & Mexicans; Intermittent acute attacks of muscle Tx: β2 blockade, acetazolamide,
usually men weakness w/ hypoK (↓P, ↓ Mg often) reduce CHO in food
Inherited: AD, α-1 DHP-sensitive Ca mutation Triggered by large CHO meals, rest post-
exercise
Hyperkalemia Pseudo Mechanical trauma during venopuncture
Increased WBC or platelet counts (leak in
tube)
Intake Unusual
Renal Primary decrease in distal delivery Acute oliguric renal failure
Acute glomerulonephritis
Primary decrease in mineralocorticoid Addison's
activity Hyporeninemic hypoaldosteronism Commonly caused by diabetes
ACE Inhibitors
Adrenal biosynthetic defects
Abnormal cortical collecting duct Intrinsic renal disease
Amiloride, spironolactone, triamterene
Cellular Cell death/ischemia Lactic acidosis
redist. Acidosis Mineral acidosis Cause K shift
*Diabetic ketoacidosis (organic) Insulin deficiency Do NOT cause K shift because of acid,
Hyperosmolality but rather because of insulin
(organic ions go in with H, so no K
needs to move out)
Toxins/drugs tetrodotoxin: found in fish
succinylcholine: anesthesia
Hyperosmolality
Hyperkalemic periodic paralysis
Insulin deficiency
Acid-Base Metabolic Disorders
Causes Findings/Notes
Saline dilution Massive NaCl infusion → dilution of HCO3 HCO3 rarely drops > 4 mEq/L
Very mild acidosis only
(aka hyperchloremic) Cl-containing acid NH4Cl ingestion
Parenteral hyperalimentation (acidic AAs)
Nl Anion Gap
Chronic ketoacidosis (or recovery
phase of DKA)
GI HCO3 loss (diarrhea, fistulae) ↓ K, ↓ pH → intracellular acidosis → ↑ renal NH3 production Urine anion gap = Na + K - Cl
→ ↑ urinary excretion of NH4Cl
Renal Tubular Acidosis (RTA) T1 - Hypokalemic Distal (MCD doesn't acidify) Occurs as a lack of appropriate response
T2 - Proximal (proximal tubule doesn't reclaim HCO3) to other acidoses
Acidosis
T4 - Hyperkalemic Distal (MCD can't secrete H & K)
Lactic acidosis Circulatory collapse, anemia, hypoxemia, metabolic blockade,
seizures
Ketoacidosis Diabetes Can cause false negative b/c
(mnemonic: KUSMALE)
Starvation β-hydroxybutyric acid not detected
Large Anion Gap
Alcoholic
Uremic acidosis Acute kidney injury Lack of ammonia in urine
(+ urinary anion gap, UAG)
comes from inability to excrete P, S,
organic acids
Overdoses Methanol intoxication (metabolized to formic acid) Increased osmolar gap
Ethylene glycol (metabolized to oxalate crystals) Increased osmolar gap
Salicylates
Exogenous base NaHCO3 (baking soda)
Citrate
IV HCO3, acetate, lactate
Initial
GI acid loss Severe vomiting
NG suction
Alkalosis
Renal acid loss Mineralocorticoid coupled w/ distal Na delivery
Post-hypercapneic alkalosis
Volume contraction ↓ EABV Only the kidney can maintain metabolic
Maintenance
(↓ GFR → net HCO3 absorption) alkalosis
K deficiency Lowers GFR → proximal & distal H secretion
↑ Aldosterone & distal Na delivery Stimulates H secretion in the presence of Na
Clinical Medicine - Kidney Injury Syndromes
Causes/Mechanisms Findings Labs Notes
Post-renal renal failure Bladder outlet obstruction (prostate) Kidney ultrasound: hydronephrosis ρ = 1.007 Obstruction from stones, sloughed papillae,
Diabetic neurogenic bladder (CNS dysf.) Protein negative blood clots
Cervical cancer Anuria or polyuria Blood negative Often reversible
Retroperitoneal fibrosis 0-3 erythrocytes/hpf Dx: kidney sonography finds hydronephrosis
0-3 leukocytes/hpf (except in retroperitoneal)
→ → Obstruction between ureters to urethra → Tx: relieve obstruction
intrarenal vasoconstriction, ischemic tubular injury,
interstitial fibrosis
Retroperitoneal fibrosis No hydronephrosis Often occurs in lymphoma
Flank/abdominal pain
Pre-renal renal failure CHF, severe vomiting → ↓ EABV → ang II & Decreased EABV BUN/Cr > 20; Una 350 Dx: BP, pulse, BUN/Cr, Urinary [Na],
function decline → azotemia thirst Hematocrit, Albumin
PE: orthostatic hypotension, ↓ skin turgor, dry ρ = 1.020
mucous membranes, low JVP Glucose negative
Protein negative
Occasional hyaline casts
Low urine Na, Cl ( 40
Uosm 100 mOsm > plasma
Intra-renal renal failure Hx: increased urination, dyspnea, edema, High urine Na, Cl (>20)
nocturia, hematuria, renal stones FENa > 1%
PE: hypertension, retinopathy, elevated JVP, U/P Creatinine & Urea 20 mEq/L Most common form of intrinsic renal failure
agents) or nephrotoxic agents (e.g. aminoglycosides, Hyponatremia FENa > 1%; Uosm 5000 U/L
to renal tubular cells → intratubular obstruction Hyperphosphatemia Heme positivity on urine dipstick in the
Hyperuricemia absence of hematuria
Metabolic acidosis
Acute muscle compartment synd.
Limb ischemia
NSAID-induced Blockage of prostaglandin negative feedback → loss Oliguria Hemodynamic form of ATN
of renal circulation → antinatriuretic & antidiuretic Rapid-onset
effects magnified Hyperkalemia
Initially low urine [Na] and Fena
Usually reversible
Vascular
Thromboembolic of renal Loss of BF → Ischemic infarction or atrophy of Wedge-shaped infarct 1/3 have hematuria Kidneys receive ≈ 20% of CO
arteries kidneys Elevated serum LAD w/o transaminase Emboli usually from mural thrombi
Dx: radioisotope renogram
Renal vein thrombosis Nephrotic syndrome → RVT Insidious onset Sometimes ↑ LAD w/o transaminase Most common in pts w/ membranous
Membranous GN most common nephropathy
Syndromes Dx: Renal vein venography, MRI
1. Asymptomatic
2. Acute: flank pain, hematuria, ↓ GFR
3. Chronic: L varicocele, ureteral notching,
asymmetry in kidney size, PE
Renal artery stenosis Renin-Ang system keeping flow, treated with ACE Taking ACE inhibitors or ARB
inhibitor → drop in pressure → ischemia Increased afferent tone or decreased flow
Anatomic: renal artery stenosis, PCKD
Functional: ↓ EABV, cyclosporin A, sepsis
Glomerular
Chronic glomerulonephritis Progressive renal failure that is insidious in onset and Small kidneys (symmetrical) Tx: Manage conservatively (because it's already
characterized by varying degrees of hematuria, Hematuria run its course)
proteinuria, & hypertension Proteinuria
(vague and all-inclusive) Hypertension
Represents end stage of other syndromes
Nephrotic syndrome Proteinuria → hypoalbuminemia → ↓ Ponc → ↓ Proteinuria (>3.5 g/24hr) ρ = 1.015 Important to identify systemic disorder that
intravascular V → 2⁰ Na retention (aldo), Hypoalbuminemia Protein 4+ may be causing dz (if excluded, ideopathic)
hyperlipidemia Edema Oval fat bodies
→ → edema, normal BP, Hyperlipidemia Fatty casts
↑ renin, AII, aldo, catechols Hypercoagulable state
Intrarenal
Infectious risk (lost antibodies) high renin, AII, aldo, catechols
1⁰ causes: MCD, FSGS, membranous glomerulopathy,
MPGN
2⁰ causes: infection, neoplastic, medications,
multisystem (diabetes, amyloid, SLE)
Acute glomerulonephritis 1⁰ Na retention → ↑ intravascular V → edema, HTN, Stable GFR (relatively) BUN/Cr > 20; Una 350 that look prerenal (low FENa, low urine Na,
congestion, hypertension etc)
1⁰: idiopathic MPGN; IgA nephropathy (10%) Hematuria (grossly visible) ρ = 1.020
2⁰:infectious (PSGN, bacterial endocarditis) Azotemia Protein 2+
HUS, TTP, SLE, cryoglobulinemia, systemic Variable proteinuria Blood 3+
vasculitis Oliguria 15-20 erythrocytes/hpf
3-5 erythrocyte casts/hpf
0-3 leukocytes/hpf
low renin, AII, aldo, catechols
Rapidly progressive Linear staining (α-GBM): Rapidly-decreasing GFR (>2 mg/dl over 3 m) Actively nephritic urinary sediment Biopsy to determine cause by IF
glomerulonephritis (-) lung hemorrhage: type I Acute nephritis Rapidly-↓ GFR (weeks to months) (linear staining, granular staining, no immune
(+) lung hemorrhage: Goodpastureäs Proteinuria deposits, etc)
Granular staining (circulating complex): Hematuria (microscopic) Little tendency for spontaneous recovery
1⁰: type 1 MPGN, IgA nephritis Acute renal failure
2⁰: is SLE, Henoch-Schönlein purpura, Often crescentic glomerulonephritis
post-infectious
No immune deposits (often α-ANCA):
Idiopathic, Wegener's, microscopic
polyarteritis nodosa, Churg-
Strauss
Asymptomatic hematuria 1⁰: IgA nephropathy; thin basement membrane Diagnosed in routine physical exam Mild renal function impairment
and/or proteinurea disease
Less common: Alport's, MPGN, mild Glomerular hematuria (gross or micro)
glomerulonephritis Subnephrotic proteinuria
Tubulointerstitial Increased urine volume BUN/Cr 20 mEq/L Na wasting
FENa > 1%; Uosm M Smaller trabeculae Most common skeletal disease
(normal bone but less of it)
Postmenopausal Estrogen deficiency → prolonged Postmenopausal 50-10% trabecular bone loss/yr Estrogen:
(type I) osteoclast activity women 2% cortical bone loss/yr ↑ FasL (osteoclast apoptosis)
End of 5th decade Usually in vertebrae & proximal femur ↓ RANKL sensitivity in osteoclasts
Senile Decreased osteoblast activity Around 30 yo 6-8% trabecular bone loss/decade Slower bone loss than type I
Osteoporosis
(type II) (M & F) 2-4% cortical bone loss/decade
Secondary Cushing's syndrome Preexisting disease
Exogenous steroid use
Immobilization
Rheumatoid arthritis (2⁰ to cytokines) -
periarticular
Paget disease Uncoupled basic multicellular unit Usually asymptomatic 1. Osteolytic phase
BMU dissoc
(BMU) Skull big and thick 2. Osteoblastic phase (burnout)
Some think paramyxovirus Limb bones distort & bend
Mosaic pattern (not organized) Usually monoosteotic (one bone)
Alkaline phosphatase ↑ in serum Polyostotic means likelihood of
osteofibroma or osteosarcoma
Pyogenic Staph. aureus (hematogenously) Children (metaphysis) Fever, pain Chronic draining tract (sinus) can result
Bacteria from ulcers (diabetic) Adults (epiphysis) Early radiographs negative Rarely: squamous cell carcinoma
Exudate penetrates cortex → elevate develops in draining duct
periosteum, periosteal osteoblasts activated
New sleeve of bone around necrotic bone
Osteomyelitis cortex (involucrum)
TB (Pott) or TB from blood → lumbar vertebrae → Pain, low-grade fever, chills, weight loss Granulomatous also from fungi
Granulomatous downward spread → kyphosis, scoliosis Can be multifocal in AIDS
Skeletal syphilis Syphilis
Bone Tumors/Tumor-like Lesions
Bones Pt. pop & location Presentation Pathology Notes (incl. Px)
Benign Osteoma Exophytic masses on skull Middle age F > M Facial asymmetry, sinus obstruction, Hamartoma Tx: excise if symptomatic
40-50 difficulty breathing, headache, auditory
disturbance
May have Gardner's syndrome
Oteoid osteoma Cortex of leg long bones Common Pain of increasing severity Well-demarcated central core/nidus Central core has PGE2 → reactive sclerosis &
10-20 (and worse at night) surrounded by zone of reactive sclerotic non-specific inflammation
M>F pain relieved by aspirin bone Tx: en bloc resection
2 cm nidus/cortex Tx: en bloc resection
Bone-Forming
15-45 years
M>F
Malignant Primary osteosarcoma Metaphysis: distal femur, M>F Pain at tumor site Physis into epiphysis Most common primary tumor of bone
proximal tibia, proximal 10-20 Late: joint stiffness/deformity Blue/gelatinous less-differentiated Frequently metastasize to lung
humerus Hereditary retinoblastoma or xray: patchy radiolucency (variation of appearance Elevated alkaline phosphatase
p53 mutations common malignant bone) Areas of hemorrhage & necrosis
Can destroy overlying cortex & elevate Tx: chemotherapy & surgery
periosteum Thoracotomy & resection of pulmonary
Codman's triangle metasteses
Secondary Pelvis Underlying bone abnormality Micro: malignant cells producing osteoid & Destroys bone
osteosarcoma Humerus (Paget's) bone Prognosis worse (pts can't tolerate
Femur 50-90 years Often high-grade chemotherapeutic protocols, surgical
(not restricted to metaphysis) M>F resection difficult at location)
Benign Osteochondroma Metaphyseal region of long 10-35 years Hard, non-painful swelling of cortex of Gross: stalk of well-differentiated bone Not true neoplasms
bones M>F metaphyseal long bones arising from cortex (benign hamartomas)
(several years' duration) Micro: cap of well-differentiated cartilage Growth ceases after sexual mat.
Tx: removal for cosmetic reasons or to stop
nerve impingement
Enchondroma Medullary cavity (metaphysis 20-50 years Slow growing & subclinical Gross: well-circumscribed lobules of Only pathologic if in phalanges
or diaphysis) genders equal Hands → pain cartilage
Cartilaginous
of long bones Micro: nodules of well-differentiated Tx: usually not required; may have surgery &
hyaline cartilage bone grafting
(difficult to differentiate from Can be malignant in Ollier disease or Maffucci
chondrosarcoma) syndrome
Malignant Chondrosarcoma Axial skeleton (pelvis, ribs) 55-80 years Dull, aching pain & tenderness Gross: in diaphysis, can fill marrow cavity Malignant tumor of mesenchymal cells
M>F (unlike benign osteochondroma) Translucent, hyaline, rubbery, nodular (like producing cartilage
Pathologic fracture is rare cartilage) 2nd most common 1⁰ malignant tumor of
Punctate foci (calcified cartilage) bone
Micro: chondroid matrix; cytologic atypia, Grade based on histology
mitotic index, cellularity
Tx: resection w/ wide margins
Giant-cell tumor Epiphyseal ends of tubular long 20-40 years Pain & tenderness at tumor site Cortex destroyed & replaced by narrow Usually benign
bones: distal femur, proximal F > M Pathologic fracture can occur layer of reactive bone Locally aggressive
tibia, distal radius Club-like expansion of bone Necrosis & hemorrhage in mass 4% of all primary bone tumors
Soft, friable, red-brown Micro: plump mononuclear cells admixed
Misc.
x-ray: soap-bubble lesions w/ multinucleated giant cells Tx: no radiotherapy
Ewing tumor Medullary cavity of tubular 10-20 Pain & tenderness at tumor site Gross: soft & tan-gray Malignant
long bones M>F Systemic: fever & weight loss Micro: ness or sheets of small round cells 22q12 ETS t(11;22)(q24;q21) or t(21;22)
(no osseous or cartilaginous matrix (q22;q12)
produced)
Prostate cancer
Metastatic
Breast cancer
Rheumatological Musculoskeletal Complaints
Patients Causes/Mechanisms Signs/Sx Notes
non-inflammatory Fractures
articular (non-articular)
Osteoarthritis F > M, age Disordered cartilage physiology Radiologic prevalence > clinical prev. Most common arthritis
(aka DJD) Peaks at 45 for hand, then Slow onset: Hands start "bothering," then knees & hips Chronic, non-inflammatory
knees & hips (over a decade) Mono or poly-articular
Collagen genes, Crepitus on exam
chondrodysplasias, Stiffness after sitting (NOT morning) 1/2 of cases: sx and radiographic findings are not
obesity, trauma/stress Bony hypertrophy: Bouchard's nodes (PIP), Hebreden's equivalent
nodes (DIP)
x-ray: loss of joint space, marginal osteophytes, sub-
chondral sclerosis & bone cysts
Osteonecrosis Trauma Ischemic death of osteocytes from Pain (groin, buttock, thigh, medial knee) Common sites: femoral head, humeral head,
Corticosteroid users blood supply loss (trauma, Rx: normal early, MRI helpful; wavy, low signals femoral condyles, proximal tibia, scaphoid, lunate,
Alcoholism corticosteroid use, alcoholism, surrounding dying bone; high signal reductions may talus, navicular, metatarsals
diabetes, SLE, Cushings, precede necrosis
hypercoagulable, hyperlipidemia, No cause identified in 30-40% of cases
sickle cell, Legg-Calve-Perthes)
mono/oligoarticular Acute septic arthritis Abnormal joint, diabetes, (see pathogens in 'notes') Fever & pain (extension > flexion) Usually knee, hip, ankle
immunosuppression, IVDA, Hematogenous seeding Swelling, tenderness, redness Usually S. aureus (IVDA, skin infxn, RA)
other infection, age, STD Direct inoculation Plain films may show fluid, joint erosions (late) Strep. (diabetes, immunocompromised)
(GC) Contiguous spread (osteomyelitis, Synovial fluid (PMNs, G+, culture) N. gon. (STD)
diabetic ulcers) WBC w/ left shift GNR (IVDA, immunocompromised, UTI)
Elevated ESR & CRP Anaerobes (IVDA, abscess, diabetes, VD)
CT/MRI fully assess joint Must be drained
Chronic septic arthritis Syphilis (Trep. Pallidum)
Lyme (Borellia burgdorferi)
Whipple (Tropheryma whilpplei)
Mycobacterial
Fungal (coccidioides, parac, blasto;
NOT histo)
Lyme Borellia burgdorferi Days: Erythema chronicum migrans Tx: penicillins/tetracyclines
Weeks: myalgia, arthralgia, meningitis, CN palsy, carditis, Ixodes ticks
AV node block, conjunctivitis, iritis
Indolent Mycobacteria
infection Fungi
Viral arthritis Exposed persons Parvovirus (≈10%) - F, symmetric, RA- (see ID lecture) Can be mono/oligo
(virus) like, resolves spontaneously
Rubella (50-60%) - symmetric
HepA (10-14%) - rash
HepB (10-25%) - severe, sudden-onset
symmetric (hands/knees)
HIV (8%) - monoarticular
Arthropod-borne - epidemics w/ rash
± spontaneous resolution
Gout 1.4% in men, 0.6% in Monosodium urate Acute, extremely painful Spontaneous resolution (3-5 days)
women (chronic hyperuricemia) Podagra - 1st MTP Recurrence mean 11 mo
Feet, ankles, heels, knees common
90% from ↓ excretion (ideopathic, Cutaneous erythema/tendinitis (like cellulitis, DVT) Elevated urate is necessary, not sufficient
CKD, drugs: EtOH, low-dose aspirin, Fever, leukocytosis (like infection) Dx: polarized LM of fluid shows blue/yellow
etc) Late: tophi in pressure points appearance w/ red filter (YUP)
10% overproduction (ideopathic, Lesch- Joint spaces preserved x-ray: soft-tissue swelling → erosions w/
Nyan) Erosions w/ overhanging edge at capsule end (not joint) overhanging edge
come late in disease
Pseudogout W > M and older Calcium pyrophosphate dihydrate Asymptomatic Dx: polarized LM of fluid shows blue/yellow
Hyperparathyroidism ("chondrocalcinosis) Psuedogout - acute monoarthritis (25%) appearance w/ red filter
Hypomagnesemia Pseudoosteoarthritis - elderly women w/ chronic
Hypophosphatasia pain/inflammation in knees, wrists, etc
Hemachromatosis Pseudoneuropathic - Charcot joint: knee/shoulder
Other crystal-induced Basic calcium phosphate
Cholesterol
polyarticular Viral arthritis (see above)
Rheumatoid arthritis F > M (3x) Unknown cause Chronic, inflammatory, polyarticular Autoantibodies: rheumatoid factor, α-cyclic
30s to 40s, increases over TNF-α & IL-1 involved Symmetric, joints tender, swollen, decreased ROM; may citrullinated peptide (CCP)
time IgM against IgG (RF) be warm and erythematous ESR, CRP
HLA-DR4 haplotype Hours of generalized morning stiffness Normochromic normocytic anemia
Synovial membrane proliferation → Characteritic joint abnormalities: Boutenniere (flexion of
osteoclast activation → pannus PIP/hyperextension of DIP), Swan-neck (flexion of Extraarticular: can have rheumatoid skin nodules
replaces chondrocytes DIP/hyperextension of PIP), ulnar MCP deviation (histiocytes & granulation tissue) on extensor
Radiograph: periarticular osteopenia, soft-tissue swelling, surfaces, vasculitis, ocular inflammation
uniform joint space narrowing, marginal erosions (which
cause disability) Additive
Seronegative HLA-B27 Ankylosing spondylitis, psoriatic Asymmetric Chronic, inflammatory oligo or polyarticular
spondyloarthropathy arthritis, reactive arthritis Often involves axial skeleton
Ankylosing M>F Inflammatory back pain (1st) Extraarticular: anterior uveitis (25-30%) - tearing,
spondylitis early adulthood Insidious onset, > 3mo durationn, morning stiffness pain, photophobia, blurry vision. corneal
Axial arthritis - pain in spine inflammation, monocular; aortitis/aortic
Enthesitis - pain @ tendon/ligament insertion to bone insufficiency/heart block; spinal cord damage
Arthritis of hips (1/3 of patients) (spinal fracture, cauda equina syndrome)
Peripheral arthritis
xray: erosion, sclerosis, and fusion of sacroiliac
joints; erosion at tendon attachment sites;
ossification of annulus fibrosis, apophyseal joitns,
intervertebral ligaments ("Bamboo spine")
Psoriatic 5-7% of pts w/ psoriasis Arthritis after years of skin disease Extraarticular: pitting fingernails, nail dystrophy,
arthritis Many forms: RA-like poly, DIP & large joint oligo, spine &
sacroiliac disease, arthritis mutilans
Reactive Recent GI/GU infection: Chlamydia trachomatis 2-4 weeks after infection → additive oligoarticular aka "Reiter's syndrome": urethritis, conjunctivitis,
arthritis Shigella/Salmonella/Campy Shigella flexniri asymmetrical arthritis arthritis
lobacter/Yersinia, Salmonella enteritidis lower > upper limb involvement
Chlamydia (may follow Salmonella typhimurium Digits of hands/feet diffusely inflamed (dactylitis) Extraarticular: keratoderma blenorrhagicum,
these symptoms) Y. enterocolitica & pseudoTB "Sausage digits" carcinate balanitis, oral ulcers, anterior uveitis,
Campylobacter jejuni Enthesitis aortitis, nail dystrophy w/o pitting
"Pencil cup" (can be Psoriatic or Reactive)
Enteropathic see reactive?
arthritis
Juvenile Ideopathic
Arthritis
Osteoarthritis (see above)
systemic SLE Characteristic rash some have discoid rash, non-tender LNs, alopecia
Inflammatory irthritis, serositis (thin pulled out), oral/nasal ulcers, pleural pain &
Abnormal CBC rub, rales, hemoptysis, renal function problems,
Glomerulonephritis sterile peritonitis, foot/wrist drop w/ paresthesia,
ANA headaches, psychosis
anti-Sm & anti-DNA
Sjögren's Syndrome Dry eyes (+ Schirmer's test)
Dry mouth
ANA
Salivary gland biopsy, parotitis
anti-SS-A(Ro), anti-SS-B(La)
Autoimmune thyroid disease
Arthralgia
Polymyositis & Characteristic rash (photosensitive shawl or V) some have alopecia (follicular atrophy & scarring),
Dermatomyositis Skin biopsy rales (ILD), symmetrical proximal weakness,
ANA
Electromyography
Abnormal MRI (muscle inflammation)
Muscle biopsy
Proximal muscle weakness
Associated malignancy
Systemic Sclerosis Sclerodactyly/Skin thickening (scleroderma, SSc)
Raynaud's some have rales (ILD), pulmonary HTN, renal
Esophageal dysmotility/GERD function problems
Telangectasiae Thickening starts in fingers, moves proximally
ILD Preceded by itching, edema
Renal impairment 'salt and peper' depigmentation, telangectasiae,
ANA calcinosis
anti-Centromere, anti-Scl-70
Systemic vasculites Palpable purpura (many types) some have asymmetric pulses, colicky abdominal
pain & melena,
Wegener Cough, hemoptysis some have hemoptysis, saddle nose
Pulmonary nodules/cavities vasculitis in kidney biopsy
Sinus/orbital granulomas
Skin ulcurs, palpable purpura
Peripheral neuropathy
c-ANCA
Arthralgias, myalgias
RPGN
PAN Limb ischemia vasculitis in kidney biopsy
Abdominal pain, hemorrhage
Mesenteric angiogram
Motor/sensory neuropathy
Tissue biopsy
Hep B
Arthralgias, myalgias
Hypertension
Giant cell Unilateral headache
Scalp tenderness
Jaw claudication
Stiff, aching shoulders & hips
High ESR or CRP
Temporal artery biopsy
Diminished or asymmetric pulses
Abnormal angiography of aorta or branches
Takayasu 20s
extraarticular Subacromial bursitis
Bicipital tendonitis
Tennis elbow Lateral epicondyle pain
Golfer's elbow Medial epicondyle pain
"Arm wrestling" pain
Trochanteric bursitis
Prepatellar bursitis
Anserine bursitis
Plantar fasciitis
Primary causes of Increased Distal Na Delivery
Diuretics
Mg deficiency Looks like 10 mg/d furosemide
Hypokalemic alkalosis,
hypocalcemia
Bartter syndrome
Thiazides
Gittelman's
Nonreabsorbed anions
Distal Na Delivery
Inhibits TAL Na absorption
Mutations in NKCC2 (A), ROMK
(B), C1CNKB (C) in TAL
DCT block of Na uptake
NCCT mutation in DCT
HCO3 (vomiting), ketoanions,
penicillins, hippurate, salicylate
Presentation/Tests Notes
Weak bladder muscle UDS (pressure flow urodynamic
(detrusor failure) studies): low voiding P & low
flow rate
Bladder stones UDS: hi void P & low flow
Radiating into bladder, vulva,
and scrotum
Urethral stricture UDS: hi void P & low flow
Bladder neck sclerosis or UDS: hi void P & low flow
contracture urethrocystoscopy
Urethral stones UDS: hi void P & low flow 50% recurrence w/in 5 years
Flank pain:
Hematuria
Infection/Fevers
Prostate Cancer DRE/PSA screening Bottom half (peripheral zone)
PSA > 10, risk of metastasis
(bone scan performed)
TRUS-guided biopsy
BPH UDS: high voiding P & low flow Most common benign tumor in M
PSA to rule out cancer Forms from transitional zone
Cause/Mechanism(s) Patient Population
Pathology/Appearance Notes
Joint Diseases
Cause/Mechanism(s) Patient Population Pathology/Appearance Signs/Sx Notes
Osteoarthritis Obesity F>M Fibrillation (shaggy) of cartilage, DIP of index finger → other digits Most common joint disease
(degenerative joint disease) Previous injury Older (85% of 70-80 yo) chondrocyte hypertrophy → Eventual knees, hips, vertebrae ADAMTS helps degrade aggrecan
Aggrecan loss matrix, thins → vascularization & No fever or malaise Asymmetrical (except in obesity)
fibroblasts come to repair → fibril cartilage Inflammation not prominent Often bilateral
Chondrocyte stress → various → sclerosis, cracks → subchondral cysts Heberden nodes (side of DIPs) Few joints severely
processes with synovial fluid Heberden nodes (DIP osteophytes) Decreased mobility
Gross: Hard, shiny articular surface of Ankylosis rarely occurs
sclerotic bone (eburnated bone)
Rheumatoid arthritis Unknown cause F > M (3x) Proliferated synovial membrane → pannus Inflammatory, multisystemic Ankylosis occurs
TNF-α & IL-1 involved 30s to 40s, increases over time formation & osteoclast activation → Fever and malaise Symmetrical lesions
IgM against IgG (RF) HLA-DR4 haplotype healing causes ankylosis Sore, stiff joints; chest pain, SOB 50% + for rheumatoid factor (IgM/IgA
Rheumatoid nodules (25%) - central Variable (waxes & wanes) & migratory against IgG Fc)
Synovial membrane fibrinoid necrosis w/ rim of epithelioid MΦ Rheumatoid nodues (palisading MΦ) Proliferation of synovial capsule
proliferation → osteoclast & lymphocytes Affects small joints, esp PIPs Inflammatory
activation → pannus replaces
chondrocytes
Lyme disease Borrelia burgdorferi Northeastern US wilderness
Gout & gouty arthritis Uric acid buildup → HGPRT deficiencies Acute: dense neutrophilic infiltrate in Tophi (crystalline aggregates) Monarticular: 50% in great toe; 90%
precipitation of monosodium Uric acid overproduction synovium & synovial fluid; long, needle- Acute arthritic episodes in instep, ankle, heal, or wrist
urate Leukemia shaped monosodium urate crystals in PMN Chronic joint deformity
Chronic renal disease cytoplasm Polyarticular in Chronic
Chronic tophaceous: synovium becomes 1) asymptomatic hyperuricemia
hyperplastic, fibrotic, thickened (pannus 2) Acute gouty arthritis
destroying underlying cartilage) 3) Intercritical" gout
4) Chronic tophaceous gout
Calcium & Bone Metabolism
Patients Cause/Mechanism(s) PTH VitD P UCa Notes/Other Key features
Hypoparathyroidism Insufficient production of PTH lo
lo hi
Can also be caused by severe Mg depletion 1,25
Pseudohypoparathyroidism Resistance to PTH (receptor) lo Short stature, brachydactyly
hi hi
Can also be caused by moderate Mg depletion 1,25 May have mental retardation, cataracts
Autosomal dominant hypocalcemia Family (AD) Activating CaSR mutation lo
lo hi
1,25
Vitamin D deficiency Poor intake Dietary lack, poor sun exposure, excess loss
Hypocalcemia
No light (intestinal malabsorption, nephrotic syndrome), lo
Renal failure, liver defect, decreased production (liver disease, 25αH def), hi 25- lo
VDR mutation kidney disease, 1α-H def OHD
→ low Vit D → low gut absorption of Ca, P
Binding/Redistribution Hyperphosphatemia
Transfusions (citrate)
Alkalosis (increases protein binding)
Rules don't apply
Acute pancreatitis
Bone uptake (osteoblastic bone metastases, bone
hunger)
Primary hyperparathyroidism F>M Too much PTH → bone resorption, gut absorption, Triad: stones (20%), bones, groans (ab)
50s-60s kidney absorption Often asymptomatic or chronic (indolent)
1/10k per year Single parathyroid adenoma (80-85%) hi hi lo/nl hi ↑ Cr (rare), ↓ radial shaft bone density (cortical)
Hyperplasia (10-15%) Tx: Surgery only cure; bone protective agents, CaSR agonist
Carcinoma, ectopic (rare)
Hypercalcemia of malignancy Humoral: PTHrp (80%) mimics PTH Fast pace (wks-mo), severe illness
hi/nl/
Local osteolytic: cytokines (20%) IL-1, 6, TNF lo lo hi Weight loss, anorexia, anemia
lo
Lymphoma: 1,25-(OH)₂D (rare) production Often hospitalized patients
Vitamin D toxicity High 1,25-D increases intestinal absorption & resorbs bone
Hypercalcemia
Granulomatous disease Granulomas or Extrarenal production by granulomatous disease or
Lymphomas lymphoma lo hi hi hi
Excess ingestion Milk cons.
Prescribed
Familial Hypocalcuric Hypercalcemia Family (AD) Inactivating mutation in CaSR blunts Ca sensor → ↑ Mimics PHPT, but…
PTH & ↑ renal Ca reabsorption 1. UCa is low
nl/hi lo lo
2. Should not be treated w/ surgery
Family history
Decreased renal excretion Thiazides, Li, milk-alkali syndrome, FHH volume
lo (hi) lo
depletion, renal insufficiency
Hypercalcemia of immobilization Hospitalized Excessive bone resorption → hypercalcemia
lo hi hi