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Case 3: Kidney issues, ECG - Coggle Diagram

- - - - Cortical/Superficial
        
        Receive ~90% of blood
        
        Found mainly in the renal cortex
        
        Loop of Henle is shorter
        
        Glomerulus is smaller
        
        Peritubular capillaries surround the nephron for reabsorption
        
        Make up about 85% of all nephrons
        
        Responsible for filtration of essential substance
        
        Plays a major role in removing waste and maintaining electrolyte balance
        
        Produces less concentrated urine because it has a shorter loop of henle
      - Juxtamedullary
        
        Receive ~10% of blood
        
        Found in the cortex-medulla junction
        
        Long loop of henle
        
        Larger glomerulus
        
        Surround by the vasa recta
        
        Make up about 15% of all nephrons
        
        Crucial for urine concentration by creating an osmotic gradient in the medulla
        
        Helps in water conservation
        
        Works with ADH to regulate water balance
  - - - Renal artery
        
        Segmental artery
        
        Interlobar artery
        
        Arcuate artery
        
        Interlobar artery
        
        Afferent arteriole
        
        1 more item...
  - - - The Glomerulus
        
        A network of fenestrated capillaries, that have high hydrostatic pressure
        
        Supplied by an afferent arterioles, and drained into an efferent arteriole
        
        Lined by the Glomerular Filtration barrier (GFB) which has 3 layers
        
        Fenestrated endothelium (Inner layer)
        
        Capillary walls that contain large pores allowing water, small solutes and ions to pass
        
        Prevents filtration of blood cells
        
        Glomerular basement membrane (Middle layer)
        
        A negatively charged meshwork of collagen and glycoproteins
        
        Acts as a charge-selective barrier, repelling negatively charged proteins
      - The Bowman's Capsule
        
        A double layered structure surrounding the glomerulus
        
        Parietal layer (outer) - Made of simple squamous epithelium, providing structural support
        
        Does not contribute to filtration
        
        Visceral layer (inner) - Made of podocytes, specialised cells with foot processes that form filtration slits, which are openings between interdigitated foot processes, acting as a size filter
        
        The slits are covered by a slit diaphragm, which is negatively charged, so it helps to repel other negatively charged molecules
        
        Outer layer of the GFB
  - - - PGC: Hydrostatic pressure in glomerulus (glomerular capillaries) [Favours UF]
        
        Due to blood pressure that is directed out of the vessel
        PGC: ~58-60mmHg
        PBS:~15mmHg
        
        Net UF pressure (PUF):
        
        ~ 17-20mmHg at afferent end
        
        ~8mmHg at efferent end
        
        Starling's equation:
        
        GFR= Kf [(PGC - PBS) - (πGC - πBS)]
        
        GFR= Kf [PUF]
        
        Glomerular Filtration constant (Kf) = ~12.5mL/min/mmHg
      - PBS: Hydrostatic pressure in Bowman’s capsule [Disfavours UF]
      - πGC: Oncotic pressure in glomerulus [Disfavours UF]
        
        Pressure due concentration gradient of dissolved proteins (higher protein conc, higher oncotic pressure)
        πGC: ~28-32mmHg
        πBS: 0mmHg (no protein in the Bowman's capsule)
      - πBS: Oncotic pressure in Bowman’s capsule [Favours UF]
  - - - PGC is affected by Mean Arterial pressure (MAP), and Arteriole vascular resistance
        
        MAP: Average arterial pressure during the cardiac cycle
        MAP = (SBP + 2(DBP)) / 3
        
        Greater MAP = Higher value of PGC
        
        Arteriole vascular resistance is determined by the diameter of the renal artery and arterioles (smaller diameter = higher resistance)
        
        Renal artery is mostly fixed in size and shape
        
        Renal arterioles are flexible and regulated by arterial smooth muscles
        
        Afferent and efferent arterioles are able to constrict or dilated in turns which can adjust RBF or GFR
        
        Narrowing of afferent arterioles:
        
        Increased afferent vascular resistance
        
        Less blood flow into kidneys and thru glomeruli
        
        Less RBF
        
        Less GFR
        (Happens when blood needs to be reserved for other organs)
        
        Narrowing of efferent arterioles:
        
        Increased efferent vascular resistance
        
        Lesser blood flow into the Kidneys
        
        Less RBF
        
        But more blood pools in the glomerulus, leading to an increase in GFR
        
        Dilation of efferent arterioles:
        
        Decreased efferent vascular resistance
        
        More blood can leave the glomerulus
        
        Less blood in the glomerulus
        
        Decreased PGC
        
        Decreased GFR
        
        Dilation of afferent arterioles:
        
        Decreased afferent vascular resistance
        
        More blood flow into the glomerulus
        
        Increased PGC
        
        Increased GFR
  - - - There are 2 main mechanisms for autoregulation of GFR and RBF
        
        Myogenic mechanism (afferent arterioles)
        
        Smooth muscles around the afferent arterioles have mechanically gated Ca2+ channel that are activated whtn the vessel wall is stretched during higher pressure
        
        Influx of Ca2+ leads to muscle contraction, leading to the vasoconstriction of afferent arterioles, and RBF and GFR reduces
        
        Tubuologlomerular feedback (TGF)
        
        Involves the Juxtaglomerular apparatus, particulary the macula densa, mesangial cells, and the juxtaglomerular cells
        
        Macula densa
        
        When GFR is too high, the concentration of electrolytes in the filtrate is too high, more Na+ and Cl - enters the macula densa, causing it to depolarise, and an influx of Ca2+
        
        Calcium influx inhibits renin release, inhibiting the RAAS, so there are no vasoconstrictiing effects on A and E arterioles
        
        The macula densa then produces adenosine, which acts on the A1 adenosine receptors in the A. arterioles, and the A2 receptors in the E. arterioles, causing them to constrict and dilate respectively
        
        When GFR is too low, the concentration of electrolytes is too low, so less Na+ and Cl- enter the macula densa, and no influx of Ca2+
        
        More renin is relased, and the RAAS is activated
        
        1 more item...
- - - - Changes in efferent vascular resistance
      - Changes of glomerular permeability
        
        KF increases during kidney diseases such as nephrotic and nephritic syndrome
        
        Nephritic syndrome:
        
        Inflammation of the glomerular structures (capillaries, podocytes, and supporting cells)
        
        The outcome would be an increase in basement membrane permeability, leading to issues such as proteinuria, haematurina, and urine cast formation
        
        Urinary casts are aggregates of proteins, cells, and other substances that form in the renal tubules
        
        Nephrotic syndrome:
        
        Deterioration or degradation of nephron structures
        
        The outcome would be leaking of plasma protein and nutrients, heavy proteinuria, heavy lipiduria, hypoalbuminemia, and generalised oedema
        
        Nephrotic syndrome is characterised by massive proteinuria, mainly albumin. When there is hypoalbuminemia, there is less oncotic pressure and the blood vessels have a reduced ability to retain water, leading to fluid leakage into the interstitial space
  - - - When MAP is low, the SNS is activated baroreceptors of the blood vessels
        
        This triggers the release of noradrenaline and Ag2, resulting in vasoconstriction of both systemic and renal arteries
        
        Mild activation of the SNS, will result in vasoconstriction of mainly the efferent arteriole, which will reduce RBF, but GFR will still be normal
        
        Intense activation of the SNS will result will result in vasoconstriction of both E and A arterioles, reducing RBF and GFR as well
  - - - The amnt of a substance X (PX) entering the kidneys must equal the amnt of substance X leaving the kidneys
        Arterial input = Venous ouput + urinary output
        
        Clearance rate of substances can vary from person to person, and is also determined by the kidney based on the importance of a substance
        
        Substances like glucose and amino acids have a very low clearance rate
        
        They are freely filtered, but extensively reabsorbed and not secreted
        
        So what is excreted is less than the filtered amount
        
        Substances like PAH have a very high clearance rate
        
        They are free filtered, but are ot reabsorbed, but are extensively secreted
        
        So whatever is excreted is higher than the filtered amount
        
        PAH is used to determine Renal plasma flow, since it equals the clearance of this substance
        RBF = Clearance of PAH
        
        Substances like Inulin and Creatinine have an intermediate clearance rate
        
        They are freely filtered, but are not reabsored or secreted, not synthesied, or metabolised, and are non-nephrotoxic
        
        So what is excreted = what is filtered
        
        Inulin and Creatinine are used to measure GFR
        
        Inulin is the gold-standsrd for measuring GFR, but
        
        It is expensive
        
        Needs to be infused into blood circulation, analyse on blood and urine concentration prior to GFR calculation
        
        Cannot be found naturally in the body
        
        Creatinine is mostly preferred to use measure GFR, but
        
        There will be an extra 10% that is secreted by tubular secretion, since creatinine is the metabolized product of creatine
        
        Luckily, the measurement of serum creatinine overestimates 10% due technical limitation and cancels oout the extra 10% from secretion
- - - - Extracellular fluid (ECF)
        20% of Body weight
        
        Interstitial fluid
        3/4 of ECF
        
        Plasma
        1/4 of ECF
      - Intracellular fluid (ICF)
        40% of Body weight
    - - ECF:
        
        Sodium ions
        
        Chlorine ions
        
        Bicarbonate ions
      - ICF:
        
        Potassium ions
        
        Magnesium ions
        
        Proteins
        
        Organic Phosphates
  - - - External balance refers to fluids and electrolytes enter and leave the body
        
        Intake sources:
        
        Drinking water (60%)
        
        Food (30%)
        
        Metabolic water (10%)
        
        Output pathways:
        
        Urine (60%)
        
        Sweat (8%)
        
        Feces (4%)
        
        Lungs (28%) - water vapor loss
      - Internal regulation involves physiological mechanisms that maintain homeostasis
        
        Cells can gain and lose osmolytes to regulate volume
        
        H2O increases leading to cell swelling
        The cell can lose Cl- and other solutes, and water will follow it due to osmosis
        This results in the regulatory volume decreasing, and fluid balance is maintained
        
        H2O decreases leading to cell shrinkage
        The cell can gain KCl, and water will follow it due to osmosis
        This results in the regulatory volume increasing, and fluid balance is maintained
    - - Fluid imbalance affects blood volume which then affects blood pressure and the perfusion of organs
        
        Fluid imbalance can cause oedema
        
        Fluid imbalance compromises the environment for cells to function optimally, leading to swelling and shrinking
  - - - Both trigger thirst senstation
  - - - Isotonic dehydration
        
        Loss of iso-osmotic fluid
        NaCl loss = H2O loss
        ICF Volume remains constant
        
        Causes:
        
        Vomiting, Diarrhoes, Haemorrhage & Burns
        
        Ileus, Ascites, & Pleural effusion
        
        Therapy:
        Volume replacement with isotonic NaCl solution
      - Hypotonic dehydration
        
        Loss of hyperosmotic fluid
        NaCl loss > H2O loss
        
        Water and OsM lost in the ECF, leading to water moving into the ICF
        
        Decreased ECF volume, ICF increased volume, lowered OsM in both
        
        Causes:
        
        Adrenal insufficiency, Diuretics, Vomiting
        
        Therapy:
        Isotonic fluid replacement
      - Hypertonic dehydration
        
        -Loss of hypo-osmotic fluid
        NaCl loss < H2O loss
        
        ECF volume decrease, and OsM increases. So water from the ICF moves into the ECF, leading to its OsM to increase
        
        Decreased ECF and ICF volume, Increased ECf and ICF OsM
        
        Causes:
        
        Osmotic diuresis
        
        Decreased ADH secretion
        
        High fever
        
        Heat stroke
        
        Massive diarrhoea
        
        Therapy:
        
        Slow water replacement (10% dextrose)
    - - Isotonic overhydration
        
        Gain of iso-osmotic fluid
        NaCl gain = H2O gain
        ICF volume remains the same, ECF volume increases
        
        Causes:
        
        Treatment of metabolic alkalosis in the presence of fluid loss
        
        Mild sodium depletion
      - Hypertonic overhydration
        
        Hyperosmotic fluid gain
        NaCl > H2O gain
        
        ECF Volume and Osm increases, so water from t he ICF moves into the ECF, and the ICF OsM will increase as well
        
        Increased ECF volume, decreased ICF volume, Increased ICF and ECF OsM
        
        Cause:
        
        High NaCl intake with less water
      - Hypotonic overhydration
        
        Gain of Hypo-osmotic fluid
        NaCl gain < H2O gain
        
        ECF gains more volume, and the OsM decreases in comparison, this leads to water from the ECF moving into the ICF, causing an increase in ICF volume, and decrease in ICF OsM
        
        Decreased osmolarity in both, and increased volume in both
        
        Causes:
        
        SIADH (Body retains more water than usual due to increased ADH secretion)
        
        Therapy:
        
        Fluid restriction and hypertonic saline
        
        ADH receptor agonist
- - - - Filtration
        
        Reabsorption
        
        Secretion
        
        Excretion
        
        The amnt excreted = amnt filtered - amnt reabsorbed + amnt secreted
        
        Net loss of substances like exogenous solutes, metabolic by-products from the blood to the tubular lumen
        
        Net gain of solutes and water from ultra filtrate from the tubular lumen to the blood
    - - Transcelluarly:
        
        Through the apical membrane of the tubular epithelial cell, moves through the cytoplasm, and exits the basolateral membrane
        
        Can be done via active transport, facilitated diffusion, or endocytosis
      - Paracellularly:
        
        The substance moves through the intercellular space between epithelial
        
        Can be done via passive diffusion, solvent drag. or charge interactions
    - - Absorption
        (Glucose)
        
        Glucose is 100% reabsorbed by the body, but around 98% of it happens in the early PCT, via the SGLT 2 and GLUT 2 transporters
        
        SGLT 2:
        
        It is high-capacity low affinity type protein transporter
        
        It is driven by secondary active transport. The electrochemical gradeint is created by the Sodium - Potassium ATPase transport.
        
        Sodium - Potassium ATPase pump sodium ions out of the cell, creating a low intracellular sodium concentration. The SGLT2 uses this gradient to transport glucose into the cell against the concentration gradient.
        
        GLUT 2:
        
        It is a carrier protein that helps in the facilitated diffusion of glucose
        
        Once glucose enters the cell, GLUT 2 carries it into the blood stream via facilitate diffusion
        
        The remaining 2% is reabsorbed in the late PCT, by the SGLT 1 and GLUT 1 transporters
        
        SGLT 1:
        
        The MOA is similar to SGLT 2 transporter, the only difference is that SGLT 1 is a high affinity low capacity type transporter
      - Secretion
        
        PCT cells secrete organic ions carried by organic transporters, which are localised on the basal and luminal membrane.
        They secrete endogenous substance (bile salts, uric acid, keto acids) as well and exogenous drugs
        
        Organic anions secreted:
        
        Drugs
        
        Penicillin
        
        Aspirin
        
        Diuretic
        
        Endogenous compounds
        
        cAMP
        
        Prostaglandins
        
        Bile salts
        
        Organic cations secreted:
        
        Drugs
        
        Atropine
        
        Morphine, quinine
        
        Amiloride
        
        Endogenous compounds
        
        Nor(adrenaline)
        
        Dopamine
        
        Creatinine (slightly)
      - Metabolism
        (Glutamine)
        
        Deamination of Glutamine generates ammonium, which is secreted.
        Bicarbonate is conveyed to blood to partially compensate the acidosis
        In CT, NH3 generated by glutamine metabolism diffuses across the membrane, binds with H ions, which yields non diffusible Ammonium, which helps acid excretion
  - - - The renal threshold for glucose is 180-200 mg/dl
      - If an amnt of a substance exceeds their Tm, some will be excreted in the urine
  - - - This results in net fluid secretion into the filtrate, since the fluid and solutes push into the filtrate
        Proteins stay in blood as it is too big to leave
    - - This results in net reabsorption from filtrate.
        Fluid reabsorbed into blood down oncotic grad
        Solutes reabsorbed into blood down solute grad
  - - - Basolateral Na/K ATPase Pump:
        
        Pumps sodium out of the PCT tubule cells in exchange for Potassium ions
        
        This maintains a low sodium concentration in the PCT tubule cells, allowing sodium from the tubular lumen to go through cotransporters via secondary active transport
        
        The low concentration is vital for SLGT, Organic phosphate cotransporters, and the sodium hydrogen exchanger, which use secondary active transport
        
        Sodium-Hydrogen exchanger:
        
        Hydrogen ions are secreted into the lumen of the PCT Tubule, in exchange for a sodium ion (the sodium ion enters the cell due to the secondary active transport)
        
        This helps to regulate the acid-base balance by removing hydrogen ions
        
        The hydrogen ion also titrates Bicarbonatae in the filtrate
        
        Hydrogen ion binds with Bicarbonate to form carbonic acid
        
        Carbonic annhydrase catalyses the conversion of carbonic acid into water and carbon dioxide, which can diffuse into the cell
        
        In the cell, Carbonic annhydrase converts Water and CO2 back into Carbonic acid
        
        Carbonic acid dissociates into Hydrogen ion and Bicarbonate
        
        Bicarbonate is transported into the interstitium via a Na/HCO3 co transporter
        
        Some Sodium can be transported paracellularly through leaky tight junctions
        Leaky tight junctions are tight junctions that have less claudin proteins, which increases ion permeability
- - - - ICF amnt of Potassium ions: 140-150mM
        ECF amnt of Potassium ions:
        3-4.5mM
        
        Impacts of Potassium imbalance
        
        Hypokalaemia:
        
        Cells become more -ve and less sensitive to depolarisation
        
        Muscle weakness -> Paralysis
        
        Abnormal neural conduction (confusion, and coma)
        
        Increased the risk of arrhythmia
        
        Hyperkalaemia:
        
        Cardiac arrhythmia
        
        Increased risk of cardiac arrest
        
        Abnormal neuronal conduction
        
        To prevent imbalance, the body has to maintain homeostasis
        
        3435 mEq of potassium is kept in tissue stored
        
        2635mmol in muscles
        
        250mmol in the Liver
        
        300 mmol in bones
        
        250 mmol in RBCs
        
        This is internal balance, since the cells provide and immediate buffer to reduce plasma pottasium. This is stimulated insulin, adrenaline, and aldosterone
        
        This is needed since the kidneys take a while to respond to increased potassium levels
        
        5 - 10 mEq is excreted through feces a day
        90-95 mEq is excreted through urine a day
        
        This is external balance, where the kidneys filters plasma to remove excess potassium to maintain homeostasis
    - - 1. Rapid changes of acid-base load or K changes in plasma
        
        Acid-base
        
        Acidosis:
        
        To lower pH, hydrogen ions are takein into the cell in exchange for potassium ions
        
        This results in hyperkalaemia
        
        Alkalosis:
        
        To increase pH, hydrogen ions leave the cell in exchange for potassium ions
        
        This results in hypokalaemia
        
        K changes in plasma
        
        Hyperkalaemia:
        
        To lower plasma potassium level, Potassium is taken into the cell in exchange for hydrogen ions
        
        This results in acidosis
        
        Hypokalemia:
        
        To raise plasma potassium, potassium exits the cell in exchange for hydrogen ions
        
        This results in alkalosis
      - 2. Plasma osmolality
        
        ECF Osmolality increase, H2O leaves the cell, leading to an increase in ICF potassium levels. Then, potassium moves out o fthe cell through potassium channels, leading to an increase ECF potassium levels
      - 3. Cell lysis (Burns, rhabdomyolysis, Chemotherapy)
        
        Cells contain around 98% of the body's potassium, when the cell is broken down, that potassium is released into the blood, increasing the risk of hyperkalaemia
      - 4. Vigorous exercise can be life-threatening if you have endocrine disorders (insulin deficiency), renal failure, and are on certain medications (B2 adrenergic blockers)
  - - - Excretion can increase to 15-80% by reducing absorption along with some tubular secretion if the body needs to excrete potassium in case of high potassium levels
      - In situations where potassium is delpeted, the kidneys can increase reabsorbtion and minimize secretions, but the amount excreted cannot be reduced that much
      - Late PCT:
        Potassium tavels to the blood by passive diffusion paracelllarly
      - Thick ascending LOH:
        Major movement is done via the Na-K-Cl cotransporter, but some can also go paracellularly
      - Principal cells in the DCT and CD:
        Excretes potassium following sodium reabsorption
        
        Net effect depends on the relative handling of potassium by principal and a-intercalated cells
      - A-intercalated cells in the CD:
        Reabsorb potassium in exchange for hydrogen
  - - - Aldosterone inserts more sodium channels into the apical membrane, and more Na/K ATPase into the basolateral membrane
        
        Sodium reabsorption increases, which generates an electrochemical gradient
        Na/K ATPase creates a steeper Potassium concentration gradient
    - - Increased urine flow rate steepens gradient for potassium exit
        
        Is counterbalanced by ADH
        
        Urinary flow rate can impact potassium excretion alone, but since potassium balance would change to any alterations in water balance
    - - Alkalosis increases potassium secretion at the kidney level, since it stimulates Na/K ATPase, and increases number of Potassium channels
      - Acidosis reduces potassium secretion at the kidney level, since it inhibits Na/K ATPase, and decrease the number of Potassium channels
  - - - Causes:
        
        Inadequate intake
        
        Diet deficient in potassium
        
        Excessive renal, GI and skin losses
        
        Diruetics, hyperaldosteronism, increased sweting, vomiting, diarrhoea
        
        Transcellular shift
        
        Insulin administration, B-adrenergic agonist, Alkalosis
      - Effects:
        
        Neuromuscular manifestation
        
        Muscle weakness, fatigue, cramps, paralysis
        
        Renal manifestation
        
        Polyuria, urine with low osmolality, polydipsia
        
        GI manifestation
        
        Anorexia, nausea, vomitng, constipation, abdominal distension
        
        Cardiovascular manifestations
        
        Arrhythmias and increased sensitivity to digitalis toxicity
        
        Metabolic alkalosis
    - - Causes:
        
        Increased intake
        
        Decreased renal elimination
        
        Decreased renal function
        
        Potassium sparing diuretics
        
        Hypoaldosteronism
        
        Transcellular shift
        
        Tissue injury
        
        Extreme exercise
        
        Acidosis
      - Effects:
        
        GI manifestations
        
        Anorexia, nausea, vomiting, intestina cramps and diarrhoea
        
        Cardiovascular manifestations
        
        V. fib, and cardiac arrest
        
        Neuromuscular manifestaitons
        
        Paresthesia and muscle cramps
        
        Weakness and tiredness
        
        Metabolic acidosis
- - - - Pre-renal: Reduction of perfusion to the kidney (70% of cases)
        Examples:
        
        Hypovolaemia
        
        Congestive heart failure
        
        Renal artery stenosis
        
        Medications:
        
        NSAIDS - causes afferent renal artery constriction
        
        ACE inhibitors - prevent efferent renal arterty constriction
      - Post-renal: Blockage of the urinary tract
        
        Blockage at the ureter:
        
        Renal cancer
        
        Renal stones
        
        Ureteric injury from surgery
        
        Extrinsic compression of the ureter from a pelvic mass or fibrosis
        All cause hydronephrosis (swelling of the kidney due to accumulation of urine as a result of outflow blockage)
        
        Blockage at the urethra:
        
        Benign prostatic hyperplasia
        
        Prostate cancer
        
        Kidney stone
        
        Bladder cancer
        
        Drugs causing urinary retention (anticholinergic drugs)
        
        Clot retention due to blood in the urethra
        
        Urethral stricture
        
        Vital test for Post renal causes is Ultrasound Kidney Ureter Bladder (KUB)
        Can identify:
        
        Hydronephrosis
        
        Kidney stones
        
        Tumours
        
        Infections
      - Renal causes: Injury to the kidney itself
        Has multiple sources:
        
        Glomerular
        
        Glomerulonephritis:
        
        Characterised by inflammation and damage to the glomeruli, allowing proteins and/or blood to leak into the urine
        
        Presents with nephrotic syndrome, nephritic syndrome, Isolated haematuria or proteinuria, AKI or CKD
        
        Tubular
        
        Acute tubular necrosis:
        
        Tubular cell death, which is secondary to prolonged poor perfusion or drugs
        
        Renders the kidneys unable to concentrate urine, causing the body to lose large volumes of poor quality urine
        
        Interstitial
        
        Acute interstitial nephritis:
        
        Inflammation of the interstitum of the kidney
        
        70% of cases are cause by raections to drugs, but can be caused by infections and systemic diseases also
        
        Presents with fever, rash, and AKI
        
        Vascular
        
        Vasculitis:
        
        Autoimmune conditions that have in common the inflammation of blood vessels.
        
        Usuallly affects multiple organs
- - - - Less common organisms:
        
        Enterobacter spp, Pseudomonas spp, and Staph aureus
      - Why E.coli?
        
        E. coli lives in the intestines and is close to the urethra especially in females
        
        Uropathogenic E. coli have adhesins like P fimbriae, which attach firmly to the lining of the urinary tract, making it difficult for them to be flushed out during urination
        
        E. coli forms a biofilm on the bladder lining, which are structured communities that make it hard for the immune system or antibiotic to eliminate them
    - - Ascending - bacteria ascend through the urethra into the bladder. Much more common in females
      - Haematogenous - Blood-borne bacteria that lead to the infect of the renal parenchyma. Common in chronic illness, suppressed immunity, overwhelming infections, and IVDU
      - Direct innoculation into the urinary tract - Cather insertion or surgery
  - - - Presents with:
        
        Dysuria
        
        Discomfort while peeing
        
        Polyuria
        
        Urinary urgency
        
        Urethral discharge (Rare)
    - - Presents with:
        
        Symptoms of urethritis plus
        
        Suprapubic pain
        
        Back pain
        
        Pelvic pressure
        
        Costovertebral angle tenderness
        
        Haematuria
    - - Presents with:
        
        Symptoms of cystitis plus
        
        Flank pain
        
        Loin tenderness
        
        Fever, chills, and malaise
        
        Nausea and vomiting
  - - - Clinical presentation:
        
        Failure to thrive
        
        Fever
        
        Apathy
        
        Diarrhoea
    - - Dysuria, polyuria, and urinary urgency
        
        Haematuria
        
        Acute abdominal pain
        
        Nausea and vomiting
    - - Mostly asymptomatic
        
        Not diagnosed as symptoms are common with age
        
        Urinary incontinence
  - - - Leukocyte esterase or nitrite is less likely to predict bacteriuria than combinations of symptoms and signs
        
        Where only one symptom or sign is present, a positive dipstick test (LE or nitrite) is associated with a high probability of bacteriuria (80%) and negative tests with much lower (around 20%)
      - When to culture urine
        
        Symptomatic women under 65 (if risk of antibiotic resistance) unless urine dipstick negative
        
        Symptomatic patients over 65 years** or if catheterised
        
        Pregnancy, for routine antenatal tests or if symptomatic.
        
        Suspected pyelonephritis and sepsis.
        
        Suspected UTI in men.
        
        Failed antibiotic treatment or persistent symptoms.
        
        Recurrent UTI.
        
        Complicated UTI.
    - - Should be reserved for those patients in whom conventional treatment has failed or those who have recurrent or unusually severe symptoms
      - Ultrasound, CT Scan, MRI, Nuclear Scan, Voiding Cystourethrogram, IV pyelography
  - - - Use an antibiotic that is active against the causative bacterium
      - Use the shortest possible course of treatment (Longer courses for complicated UTI)
      - For non-pregnant women with lower UTI, consider delaying treatment to see if symptoms resolve without antibiotics
    - - Nitrofurantoin/Trimethoprim:
        
        Non pregnant women (>16y/o)
        
        Children(>3 months to 15y/o)
        
        Men(>16y/o)
      - Children (<3months) admit under paediatric specialist and treat IV antibiotics
      - Nitrofurantoin:
        Pregnant women
      - Uncomplicated cystitis:
        
        Treat all symptomatic patients regardless of age
    - - Non-pregnant women and men:
        
        Oral: Cefalexin
        
        IV: Amilkacin, Ceftriaxone, Cefuroime, Co-amoxicalv, or Gentamicin
      - Pregnant women:
        
        Cefalexin (oral) or Cefuroxime (IV)
      - Children:
        
        <3 months: admit under paediatric specialist and treat IV antibiotics
        
        more than 3 months to 15y/o:
        
        Oral: Cefalexin
        
        IV: Amilkacin, Ceftriaxone, Cefuroime, Co-amoxicalv, or Gentamicin
    - - Between 52% and 90% of men with a UTI have been reported to have prostatic involvement (most common, benign prostatic hypertrophy)
      - Considered to be complicated because it usually results from an anatomic or functional anomaly, or from instrumentation
- - - - GFR:
        
        2 GFR values 3 months apart are required to assign a stage
        
        Stages of CKD
        
        GFR Category
        
        G1
        
        G2
        
        G3a
        
        2 more items...
        
        GFR (ml/min/1.73^2)
        
        More than 90
        
        60-89
        
        45-59
        
        2 more items...
        
        Term
        
        Normal or high
        
        Mildly decreased
        
        Mildly to moderate decreased
        
        1 more item...
        
        In the absene of kidney damage, G2 and G1 do not fulfill the criteria for CKD
      - Albuminuria:
        
        Persistent increased protein in the urine (2 positive tests over 3 or more months)
        
        Stages of CKD
        
        Category
        
        A1
        
        A2
        
        A3
        
        1 more item...
        
        30-300
        
        2 more items...
        
        Less than 30
        
        Less than 3
        
        2 more items...
        
        AER
        (mg/24hrs)
        
        ACR
        
        (mg/mmol)
        
        (mg/g)
        
        Terms
  - - - Pre-renal: Conditions that lead to presistently decreased renal perfusion
      - Renal:
        
        Renal vascular disease
        
        Glomerular disease
        
        Tubular and interstitial disase
      - Post-renal: Chronic obstructions
    - - Diabetes mellitus:
        
        Hyperglycaemia
        
        Glomerula hyperfiltration
        
        Renal hypertension
        
        Endothelial injury
        
        Proteinuria
        
        1 more item...
        
        Filtration barrier injury
        
        Mesangial matrix expansion
        
        1 more item...
        
        Mesagial injury
        
        Ischaemia
        
        1 more item...
        
        Free radical production increases
        
        Inflammatory cytokines
      - Systemic hypertension:
        
        Arteriosclerosis
        
        Decreased filtration
        
        Activates RAAS
        
        Ischamia
        
        Endothelial injury
        
        1 more item...
        
        Filtration barrier injury
        
        1 more item...
        
        Mesagial injury
        
        1 more item...
    - - Sodium and water balance
        
        Htn
        
        Increased vascular volume
        
        Heart failure
        
        Oedema
      - Potassium balance
        
        Hyperkalaemia
      - Elimination of nitrogenous wastes
        
        Uremia
        
        Coagulopathies
        
        Bleeding
        
        Pericarditis
        
        Impaired immune function
        
        Skin disorders
        
        GI manifestations
        
        Neurologic manifestations
        
        Sexual dysfunction
      - EPO production
        
        Anaemia
      - Acid-base balance
        
        Acidosis
        
        Bone damage
      - Activation of Vit D
        
        Osteodystrophies
      - Phosphate elimination
        
        Hypocalcemia
        
        Hyperparathyroidism
- - - - 65-70% of Sodium and water a reabsorbed in the PCT,, keeping the filtrate isotonic
        
        In the descending limb of LOH, water exits the tubular lumen due to the hyperosmotic medullay interstitium, concentrating the filtrate
        (1200 mOsm/L in the inner medulla)
        
        The ascending limb of the LOH is impermeable but actively reabsorbs Sodium, Potassium, and Cl ions, which dilutes the filtrate (100 mOsm/L)
        
        DCT and CD continues to reabsorb Na, but it remains impermeable to water in the absence of ADH
        The final urine reamins hypoosmotic (50-100 mOsm/L)
        
        ADH increases aquaporin channels, making the tubule highly permeable to water, causing the water to move out into the hyperosmotic medullary interstitium, which concentrates the urine.
        The final urine would be about 1200m Osm/L
- - - - Calcium oxalate:
        
        10% of cases come from Hypercalcemia and hypercalciuria
        
        55% of cases come from hypercalciuria without hypercalcemia
        
        5% of cases come from Hyperoxaluria
        
        Hyperoxaluria is a condition where excess oxalate is excreted in the urine
        
        Can be caused by genetic defects, or by excessive dietary nitake
        
        They are black or dark brown in colour with and envelope or dumbbell shape.
        
        Radio-opaque on X-Rays
      - Calcium phosphate:
        
        More likely to form in alkaline urine
        
        Hypercalcemia and hypercalciuria
        
        Hypercalciuria without hypercalcemia
        
        Hypocitraturia
        
        Hypocitraturia is acondition where there are low urinary citrate levels
        
        Ther are dirty white stones that have a wedge prism shape
      - Struvite stone (Magnesium ammonium phosphate)
        
        Formed after UTIs by urea splitting bacteria that convert urea to ammonia
        
        The resultant alkaline urine causes the precipitation of magnesium ammonium phosphate salts
        
        Staghorn shaped stone, with coffin lid crystals
      - Uric acid:
        
        50% of cases are Idiopathic
        
        Acidic urine increases the risk of uric acid stone, since uric acid is insoluble in acidic urine
        
        25% of cases are from hyperuricemia. It can come from purine rich foods such as shellfish, red meats or organ meats. It can also be caused by gout, or metabolic syndromes
        
        Red-brown in colour with rhomboid shaped crystals
        
        Radiolucent on X-Rays
      - Cystine:
        
        Caused by a rare disorder called cystinuria that causes cystine to leak into the urine
        
        When there is too much cystine, kidney stones can form
        
        Stones form at low urinary pH
        
        Yellow coloured stones with a hexagonal shaped crystal
        
        Poorly Radio opaque on X-rays
- - - - Regulated by Aldosterone
        
        Aldosterone upregulates NCC and ENaC
  - - - Aldosterone antagonists:
        
        Inhibits Apical ENaC, Potassium channels, Basolateral Na/K ATPase pumps, and ENaC activators like SGK1
        
        Promotes sodium excretion, and spares Potassium from being transported into filtrate and excreted in urine
      - Epithelial Na Channel antagonists:
        
        Antagonist to ENaC channels in the principal cells of the late DCT and CD
        
        Promotes sodium excretion