Friday, February 12, 2016

High Yield Physiology, aka "Pearls"


A collection of medical physiology topics that are considered high yield; i.e., need to know for USMLE Step 1

High Yield Physiology, aka "Pearls"

Wednesday, February 10, 2016

Heart Disease in Women





Heart disease is the No. 1 killer of American women, affecting more women than men and causing more deaths than all forms of cancer combined.  Here are some other facts: 
- Ninety percent of women have one or more risk factors for developing heart disease
- The symptoms of heart disease can be different in women and men, and are often misunderstood
- While 1 in 31 American women dies from breast cancer each year, 1 in 3 dies of heart disease
- Hispanic women are likely to develop heart disease 10 years earlier than Caucasian women
- Cardiovascular disease is the leading cause of death for African American women

Wednesday, January 27, 2016

Tachycardia - treatment with adenosine



  • Adenosine slows conduction time through the A-V node, can interrupt the reentry pathways through the AV node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff- Parkinson-White Syndrome. Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. Adenosine has a half- life of less than 10 seconds in whole blood.

ADMINISTRATION ROUTES: IV
ALTERNATIVE NAMES: Adenocor
ICU INDICATIONS:
  1. Conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome).
PRESENTATION AND ADMINISTRATION:
  • IV: Adenosine comes in a vial containing 6mg in 2mls solution
  • Compatible with the following IV fluids: Normal Saline Store at room temperature
  • DO NOT REFRIGERATE as crystallisation may occur. The solution must be clear at the time of use.
DOSAGE:
  • Adenosine injection should be given as a rapid bolus by the peripheral IV route. It should be given as close to the patient as possible and followed by a rapid saline flush (this is best achieved by using a three-way tap system) The recommended IV doses for adults are as follows: Initial dose: 6 mg given as a rapid IV bolus (administered over a 1-2 second period). Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1-2 minutes, 12 mg should be given as a rapid IV bolus. This 12 mg dose may be repeated a second time if required. Central venous administration of adenosine has not been systematically studied; however, in the ICU setting this route of administration is acceptable.
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
  • No dosage adjustment is required in renal failure or renal replacement therapy.
DOSAGE IN PAEDIATRICS:
  • Paediatric Patients with a Body Weight < 50 kg:
    • Initial dose: Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.
    • Repeat administration: If conversion of PSVT does not occur within 1-2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.
  • Paediatric Patients with a Body Weight > 50 kg: Administer the adult dose.
CLINICAL PHARMACOLOGY:
  • Adenosine slows conduction time through the A-V node, can interrupt the reentry pathways through the AV node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff- Parkinson-White Syndrome. Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. Adenosine has a half- life of less than 10 seconds in whole blood.
CONTRAINDICATIONS:
  1. Second- or third-degree A-V block (except in patients with a functioning artificial pacemaker).
  2. Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker).
  3. Known hypersensitivity to adenosine.
WARNINGS
  • Heart Block: Adenosine injection exerts its effect by decreasing conduction through the A-V node and may produce a short lasting first-, second- or third-degree heart block. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adensoine should not be given additional doses. Because of the very short half- life of adenosine, these effects are generally self-limiting.
  • Asystole and VF: Transient or prolonged episodes of asystole have been reported with fatal outcomes in some cases. Rarely, ventricular fibrillation has been reported following adenosine administration, including both resuscitated and fatal events. In most instances, these cases were associated with the concomitant use of digoxin and, less frequently with digoxin and verapamil. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving digoxin or digoxin and verapamil in combination.
  • Arrhythmias at Time of Conversion: At the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the electrocardiogram. They generally last only a few seconds without intervention, and may take the form of premature ventricular contractions, atrial premature contractions, sinus bradycardia, sinus tachycardia, skipped beats, and varying degrees of A-V nodal block. Such findings are seen in 55% of patients.
  • Bronchoconstriction: Adenosine has been administered to a limited number of patients with asthma and mild to moderate exacerbation of their symptoms has been reported. Adenosine should be used with caution in patients with obstructive lung disease or asthma. Adenosine should be discontinued in any patient who develops severe respiratory difficulties.
PRECAUTIONS
  • General: See CONTRAINDICATIONS and WARNINGS
IMPORTANT DRUG INTERACTIONS FOR THE ICU
  • Digoxin with or without verapamil use may be rarely associated with ventricular fibrillation when combined with adenosine (see WARNINGS).
  • The effects of adenosine are antagonised by methylxanthines such as caffeine and theophylline. In the presence of these methylxanthines, larger doses of adenosine may be required or adenosine may not be effective.
  • Adenosine effects are potentiated by dipyridamole (persantin). Thus, smaller doses of adenosine may be effective in the presence of dipyridamole.
  • Carbamazepine has been reported to increase the degree of heart block produced by adenosine.
ADVERSE REACTIONS
  • The half-life of adenosine is less than 10 seconds. Thus, adverse effects are generally rapidly self-limiting.
  • Body as a Whole: Apprehension
  • Cardiovascular System: Facial flushing, headache, sweating, palpitations, chest pain, hypotension
  • Respiratory System: Bronchospasm, shortness of breath/dyspnea, chest pressure
  • Digestive System: Nausea, metallic taste, tightness in throat, pressure in groin.
  • Nervous System: Lightheadedness, dizziness, tingling in arms, numbness, blurred vision, burning sensation
Critical Care Drug Manual
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Wednesday, January 20, 2016

Ask Questions



He who asks a question may look momentarily stupid
but he who does not will remain forever ignorant 

Chinese Proverb

Monday, January 18, 2016

Blood pressure & hemodynamics

Overview of Circulation





Arterial Pressure

constant capillary flow keeps gas exchange constant and also prevents "sludging" of red cells in capillaries.  Blood is like ketchup - hard to start flow when flow is stopped.

Mean arterial pressure (MAP) is calculated as 2/3 diastolic + 1/3 systolic. 120/90 MAP = 60 + 40 = 100 mmHg.  120/80 MAP = 53 + 40 = 93 mmHg.  The reason MAP is not the average of systolic and diastolic is due to the fact that, at rest, 2/3 of the time is spent in diastole and 1/3 is spent in systole.


pulse pressure = systolic - diastolic  changes with stroke volume & aortic compliance


Control of diastolic pressure
  1. heart rate  - determines "run off" time during diastole
  2. total peripheral resistance (TPR) - determines slope of "run off"






MEMORY TOOL - PQR  (ABC rule)

P = QR   (use algebra to rearrange)

very useful in understanding hypertension and hypotension (shock)

R = P/Q   for whole system

R = 8nl/pi r4         for single tube   2^4 = 16

where n is viscosity; l is length; and r is radius.  Viscosity is greater with more red blood cells.  More red cells (higher Hct) = more O2 delivery but higher resistance.

There is an optimum Hct (or hemoglobin) that is close to normal Hct.  this can go up and down with blood volume



Resistance is in series; e.g. right heart and left heart or parallel; e.g., organs of body AND  capillary beds.
adding a resistance in parallel ALWAYS lowers total resistance.
e.g.,  1/R = 1/2 +1/2 +1/2 = 3/2  so R = 2/3 = .66

added R

1/R = 1/2 +1/2 +1/2 + 1/2 = 4/2  so R = 2/4 = .5

Flow = velocity x cross-sectional area

cm3/min = cm/min x cm2/min  

student question: does density change in blood to change Reynold's No.?  N = pdv/n

ans. =  no
note that in air, changes in density can be important  (why deep divers use helium),  Helium also used clinically in patients with severe airway obstruction.


Regulation of Blood Pressure  P = QR


R
slow = hormonal
fast = neural

Q
slow = hormonal
fast = neural

Cardiac Cycle


tricuspid valve   then    bicuspidvalve   memory tool:  "try it before you buy it"



Wiggers Diagram with EKG


Right heart pressures LOW due to lower resistance of lung circulation.

Importance of low right atrial pressure  = avoids edema in organs and peripheral circulation.  Sign of right heart failure = peripheral edema (e.g., swollen ankles)






Pharmacology of EKG

Pharmacology of EKG 
Class IA
e.g. procainamide, quinidine

block Na channels and K channels

drug interactions

  • diuretics, steroids, amphotericin B = K loss
    • low K interferes with phase 3 K efflux (K channels require bound K to function normally.
  • other drugs
    • tricyclic antidepressants
Class IB
e.g., lidocaine
  • works on cells with long action potentials = ventricles, not atria
  • little or no effect on QRS or AP  (nl EKG)

drug interactions
Hyperkalemia - lidocaine  increases chance of toxicity  


Class IC
e.g., flenainide

  • effects on EKG similar but smaller than IA.
  • works on both atria and ventricles

Local Regulation of Blood Flow

Local Regulation of Blood Flow

  • autoregulation - most important in kidney, heart, and brain (not in lung)
    • MECHANISM = matching R and P to keep Q constant  
      • Q = P/R
      • myogenic reflex  (stretch activated channels if P is high; K channel activation if P is low)
    • range over which autoregulation occurs may change;e.g., chronic hypertension shifts range to higher values.

  • metabolic regulation

  • In Lungs hypoxia has opposite effect = vasoconstriction - mediated by specializes K channels that are inhibited by hypoxia = depolarization and Ca influx.

  • Flow regulation
    • hemodynamic forces






Pulmonary Edema

Pulmonary Edema





It is less confusing to think of the colloid osmotic pressure as a positive number with a minimum value of zero (NO PROTEIN).





When the rate of fluid filtration from the capillary 
into the interstitium is the rate of lymphatic removal and evaporation - no net fluid accumulation.


• However, when the rate of fluid filtration from the 
capillary into the interstitium is > the rate of lymphatic removal and evaporation - there is net 


fluid accumulation PULMONARY EDEMA.



Cardiogenic Pulmonary Edema



In a normal lung, the driving force for fluid filtration is 
~1 mmHg

• If in CHF the pulmonary capillary pressure increases 
to ~25 mmHg

• Assuming that at least initially Pi ~ 8 mmHg, plasma 
protein osmotic pressure is ~28 mmHg, interstitial 

fluid protein osmotic pressure is ~14 mmHg, and 
remains 0.98

• Then [(25 8) 0.98(28 14)] = ~ 19 mmHg






Treatment for pulmonary edema


Decrease Preload: diuretics, sit patient up in bed, n
itrates, morphine, dialysis.
Improve Cardiac Performance: Nitrates, Inotropes, 
Digoxin.
Decrease Afterload: ACE inhibitors, nitroprusside
Increase Pi: Continuous positive airway pressure, 
mechanical ventilation
Decreasing LpA, or osmotic pressure has not been 
attempted.
Non-cardiogenic Pulmonary Edema

If there is endothelial damage Lp
increases and Jv increases





Capillary endothelium loses barrier function
– Does not require change in hemodynamics
– Forces that oppose Pc decrease
– LpA increases
– leaky capillaries and increased fluid filtration!

Treatment of non-cardiogenic pulmonary edema


Treatment / Removal of offending source (infection , aspiration , inhalation)
• Mechanical Ventilation if necessary (with low tidal volumes)
• Many experimental therapies (antiinflammatory among others)


DDx Cardiogenic versus Non-cardiogenic


Underlying condition: Myocardial infarction vs. severe infection
• X-ray appearance
• Estimates of Pc (central venous pressure, BNP peptide)
• Measurement of Pc (Swann-Ganz Catheter)
• Measurement of Alveolar protein concentration (estimate of Ï€i)


Hanta virus = both cardiogenic and non-cardiogenic pulmonary edema

High altitude pulmonary edema (HAPE)

cardiogenic = pulm venoconstriction
non-cardiogenic = protein in alveolar fluid












Pulmonary Edema
into the interstitium is the rate of lymphatic 


Treatment for pulmonary edema


  • Decrease Preload: diuretics, sit patient up in bed, n
    • itrates, morphine, dialysis.
  • Improve Cardiac Performance: Nitrates, Inotropes, 
    • Digoxin.
  • Decrease Afterload: ACE inhibitors, nitroprusside
  • Increase Pi: Continuous positive airway pressure, 
    • mechanical ventilation
  • Decreasing LpA, or osmotic pressure has not been 
    • attempted.
Non-cardiogenic Pulmonary Edema

    If there is endothelial damage Lp
    increases and Jv increases






    Capillary endothelium loses barrier function
    – Does not require change in hemodynamics
    – Forces that oppose Pc decrease
    – LpA increases
    – leaky capillaries and increased fluid filtration!

    Treatment of non-cardiogenic pulmonary edema


    Treatment / Removal of offending source (infection , aspiration , inhalation)
    • Mechanical Ventilation if necessary (with low tidal volumes)
    • Many experimental therapies (antiinflammatory among others)


    DDx Cardiogenic versus Non-cardiogenic


    Underlying condition: Myocardial infarction vs. severe infection
    • X-ray appearance
    • Estimates of Pc (central venous pressure, BNP peptide)
    • Measurement of Pc (Swann-Ganz Catheter)
    • Measurement of Alveolar protein concentration (estimate of Ï€i)


    Hanta virus = both cardiogenic and non-cardiogenic pulmonary edema

    High altitude pulmonary edema (HAPE)

    • cardiogenic = pulm venoconstriction
    • non-cardiogenic = protein in alveolar fluid







    Potassium homeostasis

    Potassium

    Potassium Space is Huge

    • NaK ATPase constantly bailing Na to keep K inside
    • K "bath" used to stop hearts for surgery
    • diarrhea loss can be much higher than nl (up to 100 mEq/day)
      • creates metabolic acidosis with hypokalemia  (in most cases acidosis comes with hyperkalemia)
    K homeostasis


    • rhabdomyolysis may cause dangerous hyperkalemia
    Physiology of K homeostasis


    Death by avocado  -  response to K intake


    alpha intercalated cells and principal cells fine tune the 13% of K+ that remains in the tubule after reabsoption by the proximal convoluted tubule and thick ascending limb of the loop of Henle.  alpha cells reabsorb K+ if there is hypokalemia.  principal cells secrete K+ if there is hyperkalemia.  Also, the principal cells are the target of the adrenal medulla hormone, aldosterone, which increases Na+ reabsorption and K+ excretion.













    There appears to be a well-developed system for sensing potassium by the pancreas and adrenal glands. High potassium states stimulate cellular uptake via insulin-mediated stimulation of sodium-pump activity in muscle and stimulate potassium secretion by the kidney via aldosterone-mediated enhancement of distal renal expression of secretory potassium channels (ROMK).
    Low potassium states result in insulin resistance, impairing potassium uptake into muscle cells, and cause decreased aldosterone release, lessening renal potassium excretion. This system results in rapid adjustments in immediate potassium disposal and helps to provide long-term potassium homeostasis.



    Na and K levels Interact  --  Edelman equation

    Plasma [Na +] = Na+ + K+/TBW


    Kidneys reabsorb all filtered load of K (720 mEq/day) - most in collecting duct (principal cells)



    Bartter's Syndrome  - thick ascending limb  = same effect as loop diuretics

    Gittleman Syndrome - DCT - resembles thiazide diuretic

    Potassium sparing diuretics
    • amiloride - Naa channel blocker
    • reduced aldosterone (ACE inhibitors) or aldosterone receptor blockers (spinolactone)

    Transport in kidney

    transport in kidney

    Filtered Load = GFR x plasma concentration

    • Transport maximum = max filtered load that nephron can reabsorb = 375 mg/min for glucose
    HCO3 reabsorption in proximal tubule
    • can't cross cell membrane (neg chg)
    • combines with H+ to form CO2 & H2O
    • CO2 = non-polar molecule = diffuses across membrane


    Clearance Ratios
    • Comparison of clearance of various solutes to clearance of Inulin
    • Why inulin?
    • Cx/Cinulin = 1.0
    – Substance can be used as a filtration marker
    – Not reabsorbed, secreted or metabolized: creatinine
    • Cx/Cinulin < 1.0
    – Either the substance is not filtered OR it is filtered and subsequently reabsorbed: glucose
    • Cx/Cinulin > 1.0
    – Substance is filtered (or not) and secreted: organic acids
    – Penicillin!


    Proximal Tubule
    67% of Na and H2O reabsorption


    Loop of Henle


    Early Distal Tubule

    Late Distal Tubule


    Renal pathology

    Renal Pathology

    nephritic syndrome II

    Anti-GBM GN - Clinical Features (II)
    • Can present as:
    – pure glomerulonephritis
    – GN with pulmonary hemorrhage (more 
    often young men)

    = Goodpasture syndrome

    Anti-GBM GN - Pathogenesis
    • Immune-mediated
    • Pts make auto-antibodies against alpha 3 
    chain of collagen IV


    • Auto-antibodies bind to glomerular GBM 
    and incite inflammation


    • Pts have anti-GBM auto-antibodies in serum 
    – inc. anti-GBM antibody titer in serum



    Anti-GBM GN - Light Microscopy
    • Damage to glomerular capillary walls
    – leak of fibrin into Bowman’s space
    • Typically crescent formation
    – proliferation of Bowman’s capsule epithelial cells
    • Red cell casts in interstitial tubules

    Anti-GBM GN - IF and EM
    • By immunofluorescence
    – LINEAR deposits of IgG and C3 along glomerular basement membrane - only GN with linear staining
    • By electron microscopy
    – wrinkling of glomerular basement membrane
    – focal breaks in glomerular basement membrane
    – no deposits

    Pauci-Immune GN - (=ANCA Disease)
    ANCA = Anti-Neutrophil Cytoplasmic Antibodies
    Clinical
    • Acute renal failure - medical emergency:
    – oliguria, hematuria, red cell casts, Inc. creatinine
    • More common in adults, also occurs in children

    Pauci-immune GN – Pathogenesis I
    • Caused by circulating auto-antibodies
    • Auto-antibodies are called “Anti-Neutrophil Cytoplasmic Antibodies” (=ANCA)
    • ANCAs bind to proteins in cytoplasm of neutrophils
    • ANCAs activate neutrophils
    • Activated neutrophils incite inflammation in glomeruli

    Pauci-immune GN - Pathologic Features
    • Light microscopy:
    – Crescentic GN
    • Immunofluorescence:
    – NO GLOMERULAR STAINING (or slight non-specific staining)
    – That’s why it’s called PAUCI-immune GN


    pau·ci·ty  

    Noun
    The presence of something only in small or insufficient quantities or amounts; scarcity.
    Synonyms
    scarcity - shortage - dearth - lack - want - deficiency
    Lupus Nephritis - secondary disease to LE - most danderous aspect of LE
    Lupus Erythematosus – Definition
    • Auto-immune disease
    • More common in females than males (10:1)
    • Affects multiple organ systems → multi-system disease
    • Clinical presentation highly variable

    • Glomerulonephritis WHO class I – VI
    • Caused by immune deposits:
    – IgG, IgA, IgM, C3, C1q  all stain = only in Lupus  "Full House"

    Lupus – Criteria defined by American College of Rheumatology
    Criterion Definition -  need 3 of the following
    1. Malar rash - erythema over malar excrescences
    2. Discoid rash - skin rash
    3. Photosensitivity - skin rash after UV exposure
    4. Oral ulcers - usually painless
    5. Arthritis - joint tenderness, swelling, effusion
    6. Serositis - pleual effusion, pericardial effusion
    7. Renal disorder - Proteinuria or glomerulonephritis
    8. Neurologic disorder - Seizures or psychosis
    9. Hematologic disorder - anemia, leukopenia, thrombocytopenia
    10. Immunologic disorder - anti-ds DNA, anti Sm, antiphospholipid auto-antibodies
    11. Antinuclear antibodies - positive ANA auto-antibodies


    Alport Syndrome and Thin GBM Disease


    • Hereditary nephritis = group of familial diseases
    – Alport sydrome
    – Thin basement membrane disease (=benign familial hematuria)
    • Thin basement membrane disease:
    – asymptomatic hematuria (miscrocopic)
    – familial, but fairly common
    – diffuse thinning of GBM
    – prognosis excellent



    • Cause:
    – X-linked inheritance most common 
    – mutation in gene for alpha 5 chain of collagen IV
    • Pathogenesis:
    – abnormal assembly of collagen IV
    – altered structure and functions of GBM and other basement membranes

    Clinical features:
    – nephritis
    – nerve deafness
    – eye abnormalities (lens dislocation, corneal dystrophy)
    – express full syndrome
    – are carriers
    • Renal abnormalities:
    – hematuria (micro- or macroscopic)
    – proteinuria
    – renal failure in adult 




    Tubulo-Interstitial Diseases
    more common than glomerular diseases


    • Anatomy of normal nephron
      • each normal kidney has 800,000 -1,200,000 nephrons
    • Acute tubular necrosis
      • Definition:
        • – damage to tubular epithelial cells and necrosis
        • → acute loss of renal function (renal failure)
        • – is clinico-pathologic entity
      • Causes:
        • – ischemia (typically pre-renal) = first affects tubules
        • – toxic (intra-renal)
        • – acute tubulo-interstitial nephritis (intra-renal)
        • – urinary obstruction (post-renal)
    • Ischemia:
      • sudden drop in blood pressure (pre-renal)
        • shock (severe blood loss, burns, sepsis, acute heart failure, dehydration, prolonged diarrhea)
          • → decrease in circulating blood volume
          • → hypo-perfusion of kidneys 
          • → renal tubules oxygen-deprived
          • → necrosis of tubular epithelial cells
    • Vasculitis:
      • vascular inflammation → narrowing of renal 
      • vessels → hypo-perfusion of kidneys → → → 
    • Ischemia:
      • – tubular cell injury
        • → detachment
        • → tubular obstruction
        • → impaired urine flow in tubules
        • → increased intra-tubular pressure
        • → decreased GFR
        • → tubulo-glomerular feedback (renin-angiotensin, dec. NO, dec. prostaglandin I2)
        • → constriction of afferent arteriole supplying the nephron
        • → acute renal failure
    • Toxic:
      • drugs (e.g. antibiotics)
      • radio-contrast dyes
      • poisons (e.g. mercury, organic solvents)
      • myoglobin (released from muscles in crush injury)
      • hemoglobin (hemolysis e.g. due to transfusion reaction)
    • Acute tubulo-interstitial nephritis
      • Definition:
        • acute inflammation of tubules and interstitium - nl glomerulus
      • Two main causes:
        • Infection (typically ascending!)
        • drugs - esp. antibiotics, diuretics, NSAIDS
        • others (see Robbins p. 996, Table 20-9)
      • Clinical features:
        • begins 15 days after exposure
        • fever, blood eosinophilia, rash
        • hematuria, mild proteinuria, leukocyturia with eosinophils
        • inc. serum creatinine or acute renal failure
      • Pathogenesis: abnormal immune reaction
      • Typically: acute hypersensitivity immune reaction
        • IgE-mediated hypersensitivity (type I hypersensitivity reaction)
        • drug binds to proteins in tubular cells and becomes immunogenic (i.e. functions as a hapten)
        • idiosyncratic, i.e. NOT dose-related
      • When granulomas present (less common):
        • – delayed-type hypersensitivity (type IV hypersensitivity reaction)
    • Acute pyelonephritis
      • Very common:
        • – one of the most common kidney diseases !!!
      • Cause: bacterial infection
        • ascending from urethra and bladder, typically from pt’s own fecal flora
        • Gram-negative bacilli:
          • E. coli, Proteus, Klebsiella, Streptococcus faecalis
        • hematogeneous via bloodstream (less common)
      • Factors that promote infection and inflammation:
        • obstruction: stones, tumors, enlarged prostate, pregnancy
        • bladder dysfunction (e.g. spinal cord injury, diabetes)
        • vesico-ureteral reflux - due to incompetent vesicoureteral valve
      • Complications:
        • papillary necrosis, typically in diabetics
          • areas of gray-white necrosis in tips of renal papillae
        • pyelonephrosis
          • pus fills renal pelvis, calyces, ureter
        • peri-nephric abscess
          • inflammation spreads into retro-peritoneal soft tissue
        • sepsis → septic shock → potentially life-threatening!!!
        • Evolution into chronic inflammation with scarring
          • Chronic Pyelonephritis
            • polar scars with blunted calices
            • tubular atrophy, chronic lymphocytic infiltrate, interstitial fibrosis
    • Chronic pyelonephritis

    • Urinary tract obstruction (hydonephrosis, obstructive uropathy)
      • • Urinary tract obstruction:
        • caused by stones, tumors, enlarged prostate, others
        • → dilatation of ureter, renal pelvis, renal calices
        • → atrophy of renal cortex
        • → hydronephrosis
    • Myeloma cast nephropathy (myeloma kidney)
      • Multiple myeloma = malignant proliferation of 
      • plasma cells in bone marrow
      • Typically associated with Bence-Jones proteins in 
      • urine
        • = immunoglobulin light chains produced by malignant plasma cells
        • – appear in the urine
        • – can combine with Tamm-Horsfall protein 
        • → form casts that obstruct tubular lumina
        • – cast in tubules cause obstruction and inflammation
        • → cast nephropathy
        • Sir Henry Bence Jones in 1848:
          • – observed peculiar thermoreactivity of urine from multiple myeloma patient
          • – urine becomes turbid only between 40 C and 60 C
        • Bence-Jones proteins are monoclonal immunoglobulin light chains
        • monoclonal protein increased in serum (Mprotein, M-component, or myeloma protein)