A UTI happens when the urinary tract's normal defenses against bacteria break down, one by one.

Normal defenses — every UTI is one of these failing:

• Urine flow itself is a defense — the constant flushing action washes bacteria out before they can take hold.
• Urine's low pH and high urea concentration create conditions that inhibit bacterial growth.
• Mucosal immunity — the bladder lining secretes IgA antibody, has its own protective barrier (the urothelial barrier), and gets help from Tamm-Horsfall protein (also called uromodulin), which is secreted by kidney tubule cells in the distal loop of Henle.
• The ureterovesical junction (where the ureter meets the bladder) works like a one-way valve, preventing urine from flowing backward toward the kidneys (retrograde flow).

Pathogenesis — how an ascending infection develops, step by step:

1. Bacteria from the gut colonize the area around the urethral opening (periurethral area) — E. coli is the most common cause, and Staphylococcus saprophyticus is the second most common.
2. Bacteria climb (ascend) up the urethra into the bladder, causing cystitis, and can keep climbing to the kidneys, causing pyelonephritis.
3. Adherence and invasion: uropathogenic E. coli have hair-like structures called fimbriae that let them grip onto the cells lining the urinary tract instead of being washed away.
4. The body mounts an inflammatory response — releasing cytokines and sending neutrophils (a type of white blood cell) to the site.
5. Tissue damage follows: the mucosal lining gets irritated, swells (edema), and its blood vessels become more permeable — and this damage is what produces the classic symptoms.

Why each symptom happens:

A recurrent UTI means three or more in 12 months, or two or more in 6 months. Within that, a relapse is the same pathogen coming back within 2 weeks of treatment, while a reinfection is a new episode more than 2 weeks later. Up to 30% of septic shock cases are caused by urosepsis.

Diagnosis uses a urine dipstick: nitrites point to gram-negative bacteria (like E. coli), and leukocyte esterase points to white blood cells fighting infection — either can appear with or without visible blood. Microscopic exam can confirm this, and a urine culture identifies exactly which organism is present and which antibiotics work against it. Cystitis is diagnosed at 100,000/mL (10⁵) or more from freshly voided urine, best obtained as a midstream clean catch.

Cystitis specifically means inflammation of the bladder. It can be caused by infection, irritants, or other underlying conditions. Note the difference in scope: "UTI" is the broader umbrella term for infection anywhere in the urinary system — the bladder (cystitis), the urethra (urethritis), the kidneys (pyelonephritis), or the prostate (prostatitis).

Signs and symptoms:

• Dysuria
• Polyuria and increased urinary frequency
• Urgency
• Suprapubic and low back pain
• Hematuria
• Cloudy or foul-smelling urine
• Urinary incontinence

Not every UTI is treated the same way — the split depends on who has it and what their urinary tract looks like.

Special populations worth knowing cold:

• Pregnant women: treated even with no symptoms at all (asymptomatic bacteriuria). Cephalexin or amoxicillin-clavulanate for 7 days.
• Men: a UTI in a man is always considered complicated, and it prompts a look for prostatitis.
• Elderly: may present atypically, as confusion instead of classic symptoms.
• Children: a UTI prompts evaluation for an anatomical abnormality.

Acute pyelonephritis is a sudden, severe infection of the renal pelvis and the kidney tissue itself (parenchyma). It's an upper urinary tract infection — meaning it has climbed higher than the bladder — most often from E. coli ascending from below.

How the infection gets there:

1. Bacteria from the gut colonize the area around the urethral opening.
2. They ascend the urethra, into the bladder, up the ureters, and into the renal pelvis. Two things make this climb easier: vesicoureteral reflux (urine flowing backward from bladder toward kidney) or an obstruction.

What makes E. coli good at this — its virulence factors:

• P-fimbriae — hair-like structures that let it grip onto the cells lining the urinary tract
• Hemolysin — a toxin that damages host cells directly
• Lipopolysaccharide (LPS) — a component of the bacterial cell wall that triggers the immune system

The kidney's own cells detect the invader: toll-like receptors on renal epithelial cells recognize bacterial components, triggering release of the cytokines IL-6 and IL-8 — signals that recruit neutrophils to the site.

Once neutrophils flood in, the tissue swells and is damaged, and blood vessels become more permeable — which is what produces pyuria (pus/white cells in the urine) and hematuria (blood in the urine).

How each piece of damage shows up clinically:

• Urine culture showing significant bacteriuria — greater than 10⁵ CFU/mL.
• Pyuria — 10 or more white blood cells per high-power field.
• WBC casts — these form inside the renal tubules, so finding them means the problem is in the kidney itself, pointing specifically to pyelonephritis. That said, the course notes they may not always be present, so their absence doesn't rule it out.
• CBC showing an elevated white blood cell count.
• Imaging — renal ultrasound or CT, to look for structural abnormalities and complications like an abscess or obstruction.
• In pregnancy, renal ultrasound is first-line — it's safe (no radiation) and still detects hydronephrosis or an abscess.

Treatment:

Antibiotics, plus supportive care with adequate hydration and pain relief. Hospitalization is needed for severe cases, pregnant women, patients with significant comorbidities, or anyone who can't keep oral intake down. Follow-up includes a repeat urine culture to confirm the infection has actually cleared.

This card is now checked against your textbook. Chapter 26 arrived, and it confirms what's below. BPH still isn't covered in any webinar or slide deck, so the book is the only thing behind this card — but it is a real source now, not just "standard pathophysiology".

How it develops, in order:

1. With age, the glandular and stromal (supportive) tissue in the transition zone of the prostate undergoes hyperplasia — it grows more cells.
2. Dihydrotestosterone (DHT), converted from testosterone by the enzyme 5-alpha-reductase. Learn this pathway — it's the reason finasteride works. But be careful how you state it: your book says the cause of BPH is unknown, and that DHT's role in it "remains unclear". It calls BPH multifactorial — ageing, the balance of androgens to estrogens, long-running inflammation, and growth factors all get named. So DHT is part of the picture, not the whole answer. The cells do multiply — that part is not in doubt. What the book will not say is that DHT is the thing making them do it.
3. As the gland enlarges, it compresses the prostatic urethra (the part of the urethra running through the prostate), producing bladder outlet obstruction.
4. The bladder's detrusor muscle has to work harder to push urine past the obstruction, so it hypertrophies (thickens) to compensate. Eventually it decompensates — can no longer keep up — and urinary retention results.

Signs and symptoms — lower urinary tract symptoms (LUTS):

• Obstructive — your book calls these voiding symptoms (urine has trouble getting out): hesitancy, a weak or intermittent stream, straining, a feeling of incomplete emptying, terminal dribbling.
• Irritative — your book calls these storage symptoms (the bladder itself is irritated): frequency, urgency, nocturia (waking at night to urinate), dysuria.
• Complications: urinary retention, recurrent UTIs, bladder stones, hydronephrosis, and post-renal acute kidney injury (the obstruction backs pressure up to the kidneys).

• Age over 50 — the dominant risk factor
• Family history
• Obesity and metabolic syndrome
• Diabetes, and diet
• High blood pressure (hypertension) — this one is named outright in the book's list and was missing here
• A rising estrogen-to-testosterone ratio that comes with aging
• A sedentary lifestyle (worth knowing, but it isn't in the chapter's own list — the book says diet instead)

Treatment escalates as needed:

1. Watchful waiting for mild symptoms — monitoring, no treatment yet.
2. Alpha-1 adrenergic blockers (your book names tamsulosin and alfuzosin. Doxazosin is a real drug in this class and is used in practice, but it isn't in the chapter — so don't quote it as the textbook's answer.) relax smooth muscle in the prostate and bladder neck, giving rapid symptom relief within days. Side effects: orthostatic hypotension (dizziness on standing) and retrograde ejaculation.
3. 5-alpha-reductase inhibitors (finasteride, dutasteride) block the formation of DHT and actually shrink the gland. They are slow: several weeks before you notice anything, and a full 6 months for the maximum effect. They also drop the PSA by about 50% at 6 months and shrink the prostate by up to 25% — which matters, because a low PSA in someone on these drugs can look falsely reassuring.
4. Combination therapy (both drug classes together) is most effective for larger glands.
5. Muscarinic receptor antagonists. Once the obstruction has made the bladder muscle twitchy, these calm the urgency and frequency by blocking the receptors on the bladder muscle itself. This is in your textbook and was missing from this card entirely.
6. PDE-5 inhibitors (tadalafil), useful when erectile dysfunction is in the picture too. ⚠ This one is not in your textbook — Chapter 26 never mentions PDE-5 inhibitors, and tadalafil appears in nothing else we hold. It is real practice, just not something your book will back you up on.
7. Surgery — transurethral resection of the prostate (TURP) — for symptoms that don't respond to other treatment, or for complications. Your book lists seven reasons to operate: urinary retention that will not settle, repeated UTIs, blood in the urine that medication will not fix, failing kidneys, bladder stones, too much urine left behind after voiding, and high-pressure long-term retention. TURP is the classic operation; laser techniques have largely replaced the old open surgery.

How a stone forms, step by step:

1. Supersaturation — the urine becomes oversaturated with a stone-forming substance, such as calcium.
2. Nucleation — tiny crystals form and act as a seed, or nucleation site, where more crystal can build up.
3. Crystal retention — if urine is stagnant or flow is inadequate, those crystals aren't flushed out and stay put.
4. Stone growth — crystals keep accumulating on that seed over time until a true stone has formed.

The most common type is a calcium oxalate stone, often linked to dehydration and diet.

Risk factors:

• Genetics and demographics: family history of kidney stones, being male, ages 30–50.
• Diet and lifestyle: low fluid intake, high sodium, high animal protein, excess sugar, and high-oxalate foods (spinach, nuts, chocolate). Paradoxically, low calcium intake is also a risk factor — it increases oxalate absorption.
• Medical conditions: obesity, metabolic syndrome, gout, hyperparathyroidism, inflammatory bowel disease, gastric bypass, recurrent UTIs.
• Medications and supplements: diuretics, calcium or vitamin D supplements, antacids, topiramate.
• Urinary factors: low urine volume; high urine calcium, oxalate, or uric acid; and low urine citrate — citrate is the body's natural inhibitor of stone formation, so having less of it makes stones more likely.

• Renal colic — severe, intermittent flank pain radiating to the groin, caused by the ureter spasming as the stone tries to move through it. Sharp and comes in waves — not constant and dull.
• Costovertebral angle (CVA) tenderness.
• Hematuria — visible (gross) or only detectable under a microscope.
• Nausea and vomiting.
• Restlessness — the patient writhes around, unable to get comfortable. This is a useful clue: it's the opposite of peritonitis, where patients lie still.
• Dysuria, urgency, and frequency if the stone has moved down near the bladder (distal).
• Fever is a red flag — it suggests infection on top of the obstruction, a urologic emergency.

Diagnosis and treatment:

Non-contrast CT is the gold standard — the most sensitive and specific test for any stone type or size. Renal ultrasound or a KUB x-ray can also be used. Urinalysis shows blood, crystals, or signs of infection.

Treatment is conservative (watch and wait) for stones under 5 mm that are asymptomatic or only mildly symptomatic. Medical treatment: thiazide diuretics for calcium stones, allopurinol for uric acid stones. Stones over 5 mm, or causing severe symptoms, may need removal by lithotripsy. Treatment has four goals: manage the acute pain, help the stone pass, reduce the size of existing stones, and prevent new stones from forming.

Note: incontinence isn't covered in the webinars for this course — this comes from McCance Ch. 38 and is standard pathophysiology.

The key question for telling these two apart: is the problem in the bladder, or somewhere else?

Two more types, for completeness:

• Stress incontinence — leakage triggered by anything that raises pressure in the abdomen (coughing, sneezing, laughing, lifting), from a weakened pelvic floor or urethral sphincter. Risk factors: childbirth, menopause, obesity, prostatectomy.
• Overflow incontinence — the bladder becomes overdistended and simply dribbles over. Caused by an obstruction (like BPH) or a detrusor muscle too weak to contract (as in diabetic neuropathy or spinal injury).

• Advancing age
• Neurologic disease — stroke, multiple sclerosis, Parkinson disease, spinal cord injury
• Bladder irritants — caffeine, alcohol, carbonated beverages, artificial sweeteners
• Urinary tract infection
• Obesity
• Diabetes mellitus
• Prostate enlargement
• Prior pelvic surgery or radiation
• Smoking

Acute renal failure (ARF) is a sudden loss of kidney function that develops over hours, days, or weeks — and unlike chronic failure, it's usually reversible.

Highest risk: critically ill patients, major surgery, trauma, nephrotoxic medications, and the elderly. As the kidneys stop working, the result is fluid overload, increased potassium, and a buildup of waste products.

The four phases of ARF — memorize the numbers:

Signs and symptoms by phase:

• Onset (mostly subjective): nausea, loss of appetite, headache, lethargy, tingling in the extremities.
• Oliguric: vomiting, disorientation, edema, hyperkalemia, decreased sodium (diluted by retained fluid), rising BUN and creatinine, acidosis, heart failure and pulmonary edema, hypertension, anorexia, a sudden drop in urine output, convulsions, coma, bowel changes.
• Diuretic: rising urine output, BUN and creatinine gradually declining, hypokalemia, low sodium, a fast heart rate (tachycardia), and an improving level of consciousness.

How ARF is defined in the lab, and the urine-output terms that go with it:

• An increase in baseline creatinine of more than 50%
• A decrease in creatinine clearance of more than 50%
• Deterioration in kidney function to the point dialysis is required

The three types — organized by where the problem sits relative to the kidney:

Pre-renal — the most common cause. The damage happens before the kidney even sees the problem — something is reducing the blood flow that reaches it. Left untreated, it can progress into actual kidney (intrinsic) damage. Two mechanisms: volume depletion — there simply isn't enough blood/fluid in the system (excessive diuretics, polyuria as in diabetes, vomiting and diarrhea, burns, hemorrhage) — and hypoperfusion, where there IS enough blood and fluid, but the patient's heart or vessels can't deliver it to the kidney (decreased cardiac output from heart failure or a heart attack, and atherosclerosis).

Pre-renal pathophysiology chain: less blood flow means less blood reaches the glomerulus (the kidney's filtering unit), which drops the GFR (glomerular filtration rate — how well the kidney is filtering), which further reduces renal blood flow — a downward spiral. The very first thing the body does in response is activate the renin-angiotensin-aldosterone system (RAAS).

Intrarenal (intrinsic/structural) — the damage is inside the kidney itself, hitting one or more of its structures directly: the glomeruli, the tubules, or the interstitium (the surrounding tissue). Causes: glomerulonephritis, acute tubular necrosis, acute interstitial nephritis, rhabdomyolysis, tumor lysis syndrome, calcineurin inhibitors such as tacrolimus, and contrast dye.

Intrarenal pathophysiology: whichever structure is damaged simply stops doing its job. Since the tubules normally reabsorb sodium and water back into the body, damaged tubules mean sodium and water pass straight through and are lost in the urine instead.

Post-renal (obstruction) — the problem is located downstream of the kidney, blocking urine's path out. Most often a urinary obstruction: benign prostatic hyperplasia, kidney stones, an obstructed urinary catheter, bladder stones, or cancer of the bladder, ureters, or prostate.

Chronic renal failure (chronic kidney disease, CKD) is a progressive, irreversible loss of kidney function. It's defined by either evidence of kidney damage (pathological abnormalities) or a glomerular filtration rate below 60 mL/min present for 3 months or longer.

Three related terms, compared so they don't blur together:

• Acute renal failure — a sudden loss of kidney function from illness, injury, or a toxin. Kidney function may recover.
• Chronic kidney disease — a long, slow process where the kidneys progressively lose function, unfolding in defined stages.
• End-stage renal disease — the kidneys have completely shut down. Irreversible.

What causes chronic renal failure:

• Glomerulonephritis — the most common cause in the past
• Diabetes mellitus — now a leading cause
• Hypertension — now a leading cause
• Tubulointerstitial nephritis — now a leading cause

CKD is staged by how far the GFR (glomerular filtration rate — how well the kidneys are filtering) has fallen.

• Hypovolemia — hemorrhage, dehydration, vomiting and diarrhea, burns
• Excessive diuretic use
• Polyuria — as seen in diabetes
• Decreased cardiac output — heart failure, myocardial infarction
• Atherosclerosis and renal artery stenosis (narrowing)
• Shock and sepsis; cirrhosis
• Older age; major surgery
• Medications: NSAIDs constrict the afferent arteriole (the vessel feeding into the kidney's filter); ACE inhibitors and ARBs dilate the efferent arteriole (the vessel leading out) — both change the pressure the kidney filters with

• Prolonged hypoperfusion or ischemia — an untreated prerenal problem that's gone on too long progresses into actual tissue death: ischemic acute tubular necrosis
• Nephrotoxic medications — aminoglycosides, amphotericin B, cisplatin, calcineurin inhibitors such as tacrolimus
• Contrast dye from imaging procedures
• Rhabdomyolysis — myoglobin release from muscle breakdown
• Tumor lysis syndrome
• Glomerulonephritis — post-streptococcal, SLE (lupus), vasculitis
• Acute interstitial nephritis — drug hypersensitivity to penicillins, NSAIDs, PPIs, sulfa drugs
• Sepsis; pre-existing chronic kidney disease; diabetes; older age

• GFR below 60 mL/min for 3 months or longer — that 3-month duration is exactly what separates CKD from AKI (acute kidney injury); the same low GFR briefly is a different diagnosis.
• Persistent proteinuria together with elevated creatinine over months.
• Evidence of kidney damage on biopsy or imaging.

The lab values this course gives for the work-up:

The treatment priorities, in order:

1. Immediately treat pulmonary edema and hyperkalemia — these are the acute threats to life.
2. Remove the offending cause — most cases of AKI are reversible if the trigger is taken away.
3. Dialysis as needed, to control hyperkalemia, pulmonary edema, metabolic acidosis, and uremic symptoms.
4. Restrict sodium, water, and potassium — but, importantly, provide adequate protein.
5. Possibly add phosphate binders.

Managing chronic renal failure specifically:

• Treat whatever other conditions are present
• IV glucose and insulin, for hyperkalemia
• Sodium bicarbonate, calcium, vitamin D, phosphate binders
• Fluid restriction and diuretics
• Iron supplements, blood transfusion, and erythropoietin, for anemia
• Low-protein diet
• Dialysis after everything else has failed — the decision to start it is based more on the patient's symptoms than on the GFR number.

On treating hyperkalemia specifically: the course material states this two different ways in two different places — one slide (67) lists IV glucose plus sodium bicarbonate, another (69) lists IV glucose plus insulin. Both appear in the source. What matters for the exam is the shared underlying idea: all of these approaches shift potassium back into the cell — they don't remove potassium from the body.

Once the kidneys can no longer clear waste, its effects reach almost every organ system — this is uremic syndrome.

This is the course's key mechanism chain — walk it through in order, because each step causes the next.

1. With a diseased kidney, the enzyme needed to activate (utilize) vitamin D is absent.
2. Calcium absorption from the gut depends on that active vitamin D — so without it, calcium absorption falls, producing hypocalcemia (low blood calcium).
3. To compensate for low blood calcium, the body starts pulling calcium out of the bone.
4. But that calcium doesn't come out alone — it comes out with phosphate bound to it, so phosphate rises too.
5. Result: the bone becomes demineralized (weaker), leading to pathological fractures, and the released calcium/phosphate ends up depositing as vascular calcification in the myocardium, joints, eyes, and brain.

Treatment: calcium, vitamin D, and phosphate binders. Avoid antacids and magnesium.

Note: the course also credits this same chain with causing secondary hyperparathyroidism, listed among CKD's endocrine complications later in this unit — the source doesn't spell out the parathyroid-level step, just this sequence and that outcome.

Note: this topic isn't covered in the Week 4 webinar — it's standard pathophysiology.

• Decreased lipoprotein lipase and hepatic lipase activity — enzymes that normally break down triglycerides, so with less activity, triglyceride clearance is impaired.
• The resulting pattern: increased triglycerides, decreased HDL (the "good" cholesterol), and a buildup of VLDL remnants and small dense LDL particles.
• Insulin resistance, common in CKD, makes lipid handling worse.
• Proteinuria and nephrotic syndrome (losing protein through the kidneys) push the liver to make more lipoprotein, to compensate for the protein loss.
• Chronic inflammation and oxidative stress.
• Medications — corticosteroids and immunosuppressants.

Note: the Week 4 deck covers how ACE works in general, but not its kidney-protective role specifically — that part is standard pathophysiology.

Background — how ACE fits into blood pressure regulation:

Angiotensin-converting enzyme (ACE) is central to the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and fluid/electrolyte balance. It's made by the lung, but does its actual work — activating angiotensin I — in the kidneys, mainly in the proximal tubules.

How ACE inhibitors actually protect the kidney:

ACE inhibitors and ARBs dilate the efferent arteriole (the vessel carrying blood out of the glomerulus, the kidney's filtering unit). Widening that outgoing vessel decreases the pressure inside the glomerulus, which decreases proteinuria, which slows the progression of kidney disease. This protective benefit happens independent of any blood-pressure-lowering effect the drug also has.

Especially indicated in diabetic nephropathy, proteinuric CKD, and CKD with hypertension.

Cautions to know:

• A transient rise in creatinine is expected when starting these drugs — a rise of up to roughly 30% is considered acceptable, because it reflects the hemodynamic change described above, not new kidney injury.
• Hyperkalemia risk — potassium needs to be monitored.
• Contraindicated in bilateral renal artery stenosis (narrowing of both kidney arteries) and in pregnancy.
• Can precipitate acute kidney injury in patients who are volume-depleted.

Cardiovascular — the leading cause of death in CKD:

• Hypertension — both a cause of CKD and a consequence of it, driven by RAAS activation plus sodium and water retention
• Arrhythmias — from hyperkalemia and other electrolyte shifts
• Pericardial effusion and uremic pericarditis (fluid and inflammation around the heart)
• Heart failure and left ventricular hypertrophy (a thickened heart muscle)
• Peripheral edema
• Accelerated atherosclerosis and vascular calcification

Endocrine:

• Stunted growth in children
• Amenorrhea and male impotence — reproductive dysfunction and infertility
• Increased aldosterone secretion
• Impaired glucose levels, related to disrupted carbohydrate metabolism and insulin resistance
• Thyroid and parathyroid abnormalities — including secondary hyperparathyroidism, from the vitamin D chain covered earlier in this unit (low vitamin D → low calcium → the body pulling calcium out of bone)
• Decreased erythropoietin production, leading to anemia

Azotemia is the lab finding: elevated nitrogenous waste products in the blood, specifically increased BUN and creatinine. On its own it can be asymptomatic — the numbers are off, but the patient may feel fine.

Uremia is azotemia plus the clinical syndrome — the system-by-system symptoms (covered under uremic syndrome) that show up once those wastes have actually built up throughout the body.