Principles of Diagnostic Medicine I · Exam 1 — Study Guide

1 · Principles of Laboratory Diagnostics

1.1 · Objectives a & b — The role of testing, and counseling the patient

Diagnostics are tools to gain additional information, used in conjunction with a thorough history and physical examination — not in place of them. They are not necessarily therapeutic, though a blood culture that returns sensitivities certainly can be.

Counseling is framed as error reduction, not courtesy. Patients who are informed and understand the plan are more likely to be compliant, and compliance is what makes the result meaningful. Education covers the testing process, their questions, and the anticipated timeline for results.

1.2 · Objectives c & d — The three phases

Each phase has its own guidelines and standards, and each has its own characteristic failures.

Variables that can affect results: patient preparation · current drug therapy · time of specimen collection · physical activity · hydration status · age · sex · body mass index.

1.3 · Objective e — Collection tubes and the order of draw

1.4 · Objective f — Stool, blood, sputum and throat studies

1.5 · Objectives g, h & j — Point-of-care testing

Definition: medical testing completed outside the centralized laboratory, at or close to the site of patient care. Also called near-patient, remote, satellite laboratory testing, or rapid diagnostics. Traditional testing is multi-step and delays treatment; this brings the laboratory to the patient.

1.6 · Objective i — Qualitative versus quantitative

Non-instrumental point-of-care testing does not rely on instrumentation to interpret the result — urine pregnancy, coronavirus tests, fecal occult blood. Handheld equipment is easy to carry, one to two steps, few data points. Benchtop devices are stationary, multi-step, multiple data points. Both usually need reagents and consumables.

1.7 · Objectives k & l — Quality assurance and regulation

Clinical Laboratory Improvement Amendments (CLIA) — federal guidelines setting minimum quality standards for testing human samples at all types of sites. It began in the late 1960s after problems in the cytology laboratories reading Papanicolaou smears.

1.8 · Objective n — Screening versus diagnostic

1.9 · Objectives m & o — Sensitivity, specificity and predictive value

Then she reversed it. A shark-bite detector, same 95% and 95%: in Florida a positive has a reasonable chance of being real; in Michigan, where shark bites are vanishingly rare, most positives are false. The tests are identical. The pre-test probability is what changed.

2 · Principles of Medical Imaging

2.1 · Objective a — Fundamental properties & the diagnostic approach

Wilhelm Röntgen discovered x-rays in Germany in 1895 and took the first Nobel Prize for Physics for it in 1901 — which is why the technique is still called roentgenography. Every modality since answers the same four questions before it is ordered:

A conventional radiograph is an image made with ionizing radiation and without added contrast such as barium or iodine. It needs a source, a way to record the image and a way to process it; radiation and light strike a photosensitive surface, producing a latent image that is processed to become visible. Radiographs are quick, inexpensive and obtainable anywhere, which is why they are the most widely obtained imaging studies — against a limited range of densities and a reliance on ionizing radiation, albeit at relatively low dose.

2.2 · Objective b — The modalities, one at a time

2.3 · Objective c — Which study for which structure

2.4 · Objective d — Density, contrast & the Hounsfield scale

The vocabulary. Radiolucent and hypodense both mean the image looks darker, because more x-ray photons passed through and less was absorbed. Radiopaque, hyperdense and radiodense all mean it looks whiter, because less passed through and more was absorbed. Radiation itself is measured in millisieverts and milligrays.

A computed tomography image is a matrix of thousands of tiny squares — pixels — each assigned a number from −1000 to +1000 in Hounsfield units, according to how much of the beam that point absorbed. Water is zero by convention and everything else is placed relative to it.

2.5 · Objective e — Positioning & the imaging planes

Projections are named in the direction the beam travels, from what it strikes first to the most distal portion. So posterior-anterior means the beam enters the back and leaves the front.

For computed tomography, nuclear medicine and magnetic resonance the patient is supine, and traditional images are transverse sections viewed as if you were looking at the patient's feet — so the patient's left side is on the reader's right. Ultrasound has dozens of positions depending on the structure and the complaint, most of them some variety of supine.

2.6 · Objective f — Risks & benefits of radiation exposure

Dose is ionizing energy absorbed per unit of mass, expressed in grays or milligrays — one gray is one joule per kilogram — and often as an equivalent dose in sieverts or millisieverts. For the x-ray radiation used in computed tomography scanners, one millisievert equals one milligray, which is why the table above can label a single column with either.

Nuclear medicine is different in kind, not just in amount. In every other modality the machine is the source and the exposure stops when the study stops. In nuclear medicine the tracer is inside the patient, so for a while the patient is the source — they can briefly expose other people. That is the one radiation fact unique to these studies.

2.7 · Objectives g & h — Contrast media, contraindications & safety

Contrast is used most often to image arteries or veins, and to delineate and characterize masses — neoplastic against benign, infectious abscess against cyst. It also shows inflammation, increased blood flow and increased cellular or metabolic activity, and outlines luminal structures when given by mouth or as an enema. It can be injected into joints (arthrogram), into the central nervous system (intrathecal) and into the bladder (retrograde pyelogram). The deck calls the dyes “technically radioactive” and names cancer as a risk factor for all contrast material. That is not accurate: iodinated and gadolinium agents are radiopaque, not radioactive, and are not carcinogenic themselves. The cancer risk of a contrast study comes from the ionizing radiation of the x-ray-based technique (radiography, fluoroscopy, computed tomography); only nuclear medicine tracers such as technetium-99 are radioactive.

2.8 · Objective i — Working with the radiology team

• The radiologist has not seen the patient. Whatever you give them is what guides the read, so give as much relevant clinical information as you can.
• A vague report is a conversation, not a dead end. Contact the radiologist and discuss the patient.
• If you do not know which study to order, say what you are looking for. They can guide the choice; that is what the relationship is for.
• Imaging several regions may mean several orders — magnetic resonance of brain, cervical spine, thoracic spine and lumbar spine is four requests, not one.

3 · Diagnostic Testing for Dermatologic, Ophthalmologic and ENT Disorders

3.1 · Objective a — Ask the question first

Most skin disease is diagnosed by history and visual inspection, with office testing added only for uncertain diagnoses. Every test should answer a specific clinical question, and four factors govern which one you pick: cost, availability, invasiveness and diagnostic yield.

In the lecture she put it as “anytime you’re worried about anything that’s a malignancy, tissue is the issue — you need to figure out what the cell line is.” The closing rule of the whole lecture: always choose the least invasive test that answers the clinical question.

3.2 · Objectives a & c — Bedside microscopy and the potassium hydroxide preparation

The three bedside tests are potassium hydroxide, Tzanck and Gram stain. All three are quick, inexpensive, and both sensitive and specific; both limitations are human — operator skill and sampling technique.

Indications: tinea corporis, pedis or cruris; onychomycosis; cutaneous candidiasis; intertrigo. Procedure: scrape with a small scalpel blade onto a glass slide, add one drop of 20% potassium hydroxide, lower the cover glass to exclude bubbles, blot the excess with gauze, then survey at 10× with the condenser lowered to reduce illumination so epithelial cells become visible, and examine anything suspicious at 40×.

Sensitivity depends on adequate scraping, and a clinical-only diagnosis can misidentify a fungal infection — which is the argument for doing the test at all.

3.3 · Objectives d & e — Biopsy, the melanoma rule, and soft tissue infection

The melanoma rule. A narrow excisional biopsy with 1–3 mm margins, taken to a depth that avoids transecting the base so Breslow depth can be measured. Acceptable excisional methods are fusiform or elliptical, punch, and deep shave or saucerization — all must go below the lesion. A partial or superficial shave is acceptable only when suspicion is low, and it may underestimate Breslow depth; facial, acral and very large lesions are named here too.

Do not confuse these millimeters with the centimeters in CMS I Lecture 9. 1–3 mm is the DIAGNOSTIC biopsy margin that establishes Breslow depth; 0.5–2 cm is the definitive RE-EXCISION margin that follows once the depth is known.

Soft tissue infection. Point-of-care ultrasound reliably separates the two: cellulitis shows dermal thickening, increased echogenicity and cobblestoning (which the deck footnotes as non-specific, since venous stasis does it too); an abscess shows a hypoechoic or heterogeneous collection, possibly with debris or septations, and posterior acoustic enhancement. Computed tomography and magnetic resonance are reserved for deep-space infection, necrotizing infection, foreign body and gas, and contrast magnetic resonance best defines the extent of tissue damage.

3.4 · Objective b — Skin and wound cultures

Culture purulent lesions, sampling pus from abscesses, carbuncles and furuncles. Empiric treatment without culture is reasonable in typically presenting, uncomplicated cases. Do not culture an inflamed epidermoid cyst. Consider culturing a non-healing or chronic wound when the patient is immunocompromised, when methicillin-resistant Staphylococcus aureus is suspected, or after treatment failure.

The Levine method. Clean the wound with sterile water or saline, NOT an antimicrobial solution. Identify 1 to 2 cm of clean wound tissue. Rotate the applicator for five seconds with enough pressure to express fluid from the tissue. Do not sample exudate, eschar or necrotic material.

Culture buys you organism identification plus susceptibilities. Its limits: superficial swabs are prone to contamination and colonization and may not correlate with deep infection, so in complex wounds — diabetic foot ulcers, pressure ulcers — a deeper tissue biopsy or aspirate gives higher yield.

3.5 · Objective f — The four ophthalmic tests

The examination runs on VVEEPP: visual acuity, visual fields, external exam, extraocular movements, pupils, pressure.

Optic disc cupping. Normal cup-to-disc ratio is about 0.3; glaucomatous injury gives greater than 0.7. The healthy disc has a small central cup with a robust neuroretinal rim; the glaucomatous disc is enlarged, deeply excavated, with an undermined rim and lamina cribrosa collapse. Excavated, not merely pale, is what distinguishes glaucoma from other optic atrophies.

Ocular hypertension versus glaucoma: raised pressure with no optic damage and normal fields is ocular hypertension, a risk factor. Add optic nerve damage and it is glaucoma.

3.6 · Objective g — Throat, hearing and the middle ear

A negative rapid test in a child should be confirmed by culture; this is not routinely required in adults. And do NOT use antistreptococcal antibody titres to diagnose acute pharyngitis.

Audiometry quantifies the degree and type of hearing loss — conductive versus sensorineural — after abnormal examination findings. Indications: suspected or confirmed loss, persistent otitis media with effusion, and asymmetric loss, to screen for retrocochlear pathology. An air–bone gap of 10 dB or more correlates with middle-ear fluid; a primary-care fail is more than 20 dB hearing level at one or more frequencies.

Screening presents tones at the upper limits of normal hearing — 25–30 dB for adults, 15–20 dB for children. A threshold search finds the softest sound heard at each frequency 50% of the time. On the audiogram, intensity is on the vertical axis, right ear is a red circle and left ear a blue cross. Bone conduction uses a device vibrating through the forehead or mastoid. In the lecture she added the clinical shape of it: we lose the high frequencies first, which is the pattern of presbycusis and sensorineural loss.

Tympanometry varies air pressure in the external canal while measuring reflected energy from a tone — the less compliant the system, the greater the intensity reflected back. Pressure runs along the horizontal axis and compliance the vertical, with a normal peak at 50 mm H₂O.

3.7 · Objectives h–l — Head and neck imaging, and putting it together

Blow-out fracture: air in the orbit (orbital emphysema), a fracture of the orbital floor, and soft tissue extending down into the top of the maxillary sinus. Tripod fracture: diastasis of the frontozygomatic suture, a fracture of the orbital floor with orbital emphysema, and a fracture through the lateral wall of the maxillary sinus, which fills with blood.

Deep neck infection. Contrast CT of the neck asks three questions: is there a drainable abscess, is the airway compromised, and is it spreading towards the mediastinum. Magnetic resonance adds value for intracranial extension, vascular thrombosis (Lemierre) and osteomyelitis. Her framing in the lecture, off her own peritonsillar abscess story: “if you were worried about a deep neck infection, you want to know about abscess, you want to know about airway, and you want to know about spread.”

The four questions to ask about any test: what does it evaluate well, when do we order it, what are its strengths and limitations, and how do the results confirm the condition. She added a fifth in the lecture: “what is our next step if it doesn’t tell us?” — and only then do cost, availability and urgency enter.

4 · Complete Blood Count and Hematology Diagnostics

4.1 · Objectives a & f — What is on the panel, and which one to order

A complete blood count reports on the hematologic system and other organ systems. It contains the red cell count, hemoglobin, hematocrit, blood smear, platelet count and mean platelet volume; the four red cell indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width); and the white cell count with differential.

The deck's warning is practical: know which one you are clicking, because the two give different values.

4.2 · Objective e(ii) — The white cell lines

Normal white cell count is 4,500–11,000 cells/µL. Below is leukopenia, above is leukocytosis. White cells fight infection, migrate to injury by chemotaxis, phagocytose foreign organisms, and produce and distribute antibodies.

Steroids raise the neutrophil count by demargination — the deck spells out the mechanism: they cause neutrophils to detach from the blood vessel wall and enter the main bloodstream. And folate and B12 lower it because both are needed for the marrow to function.

Granulocytes (neutrophil, eosinophil, basophil) have distinctive cytoplasmic granules holding enzymes, proteins and toxic substances. Agranulocytes (monocyte, lymphocyte) have none, and a non-lobular nucleus. Monocytes differentiate into macrophages or dendritic cells — Kupffer cells in the liver, alveolar macrophages in the lung, Langerhans cells in the skin. Lymphocytes are T cells, B cells and natural killer cells, and the complete blood count does not tell them apart.

4.3 · Objective d — Absolute counts, and grading neutropenia

A percentage means nothing without the total. The general form is absolute count = total white cell count × that type's percentage ÷ 100, and it works for every line. For neutrophils there is one twist: bands count WITH the neutrophils.

Worked example (the deck's own): a white cell count of 6,000/µL with 40% neutrophils and 5% bands gives 6,000 × (40 + 5) ÷ 100 = 2,700/µL. When the count is written in thousands, the equivalent form is 10 × WBC(thousands) × (%neutrophils + %bands).

The number only means something once you can place it in a band — which is what the next figure is for, and it is nowhere in the slide text.

4.4 · Objective e(iii) — Platelets

Platelets form in the bone marrow from megakaryocytes, which break into fragments — so they are not really cells. Lifespan 7–10 days. Primary role is hemostasis, defined by the deck as stopping the bleeding and repairing damaged vessels; they also contribute to coagulation, vascular integrity, inflammation, immune defense, wound healing and thrombosis.

Risk of hemorrhage increases below 20,000. Note the oddity worth holding: iron deficiency raises platelets while lowering red cells.

4.5 · Objectives b & c — Hemoglobin, hematocrit and the four indices

Hemoglobin is the amount of hemoglobin in a volume of blood. Hematocrit is the percentage of that blood which is red cells — packed cell volume. The rule of thumb: hemoglobin × 3 = hematocrit.

All three of red cell count, hemoglobin and hematocrit are raised by the same three things — polycythemia vera, chronic hypoxia (chronic obstructive pulmonary disease, sleep apnea, high altitude) and dehydration — and lowered by blood loss, nutritional deficiency, marrow disorders, chronic kidney disease, cancer and dilution. Hematocrit adds smoking and hypoventilation to the raised list, and hemolysis to the lowered one.

The deck is careful about one thing: the red cell COUNT does not accurately measure oxygen carrying capacity and is not directly used to diagnose anemia, though it is still used in evaluating it.

MCH and MCHC differ only in their denominator — the red cell count versus the hematocrit — and that is the whole difference between “per cell” and “per volume”. MCHC is the automated screening flag for hereditary spherocytosis and other hyperchromic or dehydrated red cell states.

Hypochromic cells have central pallor greater than one third of the cell diameter (MCH <27, MCHC <32); normochromic is exactly one third; hyperchromic is a deeper red with MCH >33 and MCHC >36, seen in spherocytes.

4.6 · Objective e(i) — Red cell morphology

The deck sorts morphology four ways: size, hemoglobin distribution, shape variation (poikilocytosis) and inclusions with cell distribution. Start with size, because that is also where the anemia algorithm starts.

The two spiky cells are the pair people confuse, so learn them against each other.

Acanthocyte: irregular spikes, no central pallor, liver disease — from abnormal lipid metabolism or membrane change. Echinocyte: regularly spaced blunter projections right around the cell, central pallor preserved, renal disease.

Schistocytes are fragments — helmet, horn, triangular and microspherocyte forms — usually microcytic and lacking central pallor. Hemolysis, mechanical trauma (mechanical heart valves), medications (cyclosporine). Automated counters may count them as platelets, which can make a platelet count look falsely reassuring. Sickled cells (drepanocytes) are thin crescents with no central pallor and dense hemoglobin, formed under low oxygen tension.

Spherocyte: perfectly round, central pallor lost, often smaller than normal — hereditary spherocytosis. Target cell (codocyte): a dark circle inside the central pallor, from redundant cell membrane — post splenectomy and liver disease. Teardrop cell (dacrocyte): formed in marrow infiltrated by scar tissue or tumor — bone marrow disease.

Basophilic stippling is ribosomal RNA in blue-black dots spread evenly through the cytoplasm — lead poisoning. A Howell-Jolly body is a single dark purple residual nuclear fragment; the spleen normally removes them, so finding one means splenic dysfunction or asplenia — which is why target cells turn up in the same field.

Heinz bodies are the easiest thing in this lecture to miss. Denatured hemoglobin at the cell periphery, in G6PD deficiency — and they require a supravital stain (new methylene blue). They are invisible on the routine Wright stain used for the rest of the differential, so nobody will report them unless you ask.

Rouleaux is stacking like rows of coins, because raised serum proteins neutralize the negative surface charge that normally keeps red cells apart — multiple myeloma, liver disease. Agglutination is disorderly clumping from antibodies bridging the cells — transfusion reactions. Different pattern, different mechanism, different diagnosis.

4.7 · Objectives g & h — Working up an anemia

Four steps, and the notes say to do them simultaneously: assess the clinical presentation; check the complete blood count and chemistry panel; determine the mean corpuscular volume; check the reticulocyte count. Look at the peripheral smear if you can get one. A decreased reticulocyte count means underproduction; an increased one suggests hemolysis or blood loss — and the count is most useful when it is very high or very low.

Intrinsic hemolysis is a defect in the red cell causing premature splenic removal; extrinsic is mechanical stress, immunologic destruction or inflammatory injury from outside. Macroovalocytes and hypersegmented neutrophils are what mark a macrocytic anemia as megaloblastic; without them, think chronic liver disease or acute hematologic malignancy.

The iron transport analogy on the hand-drawn slide is worth keeping: the bus is transferrin (carries iron), the bus stop is ferritin (stores it, and can be measured because it sits outside the marrow), the home is hemosiderin (storage that cannot be measured), percentage saturation is total iron binding capacity (how many can sit on the bus), and the school is the red blood cell.

Two things in that algorithm are easy to walk past. Iron deficiency appears in BOTH the microcytic and the normocytic branches, which is why iron studies get obtained even when cell size is normal. And in the microcytic branch you obtain iron studies in all individuals, because a concomitant iron deficiency can affect hemoglobin analysis and hide a thalassemia.

In the normocytic branch, the reticulocyte count splits it three ways: high retics → hemolysis, sickle cell, acute hemorrhage. Low retics with low white cells or platelets → leukemia, metastatic malignancy, aplastic anemia. Low retics with normal or high white cells and platelets → chronic infection or inflammation, malignancy, chronic renal disease, endocrine dysfunction.

5 · Chemistry Panels, Renal Function and Electrolytes

5.1 · Objective a — What is on which panel

A chemistry panel is a blood test measuring metabolites, electrolytes and kidney markers, and in its expanded form liver and protein markers as well. It gives a snapshot of chemical balance, metabolism and organ function. Reynolds' framing: a panel is like a group of consultants — you can call on them individually, but you are meant to read them as a whole.

Chem-7 versus chem-8 is calcium — the chem-8 includes it. The comprehensive panel's addition is the liver panel plus total protein and albumin. Order the comprehensive one when you need a fuller picture of liver and nutritional protein status; a basic panel is enough for electrolytes, glucose and renal screening.

Grouped by what they tell you: metabolic fuel — glucose; electrolytes and acid-base — sodium, potassium, chloride, bicarbonate; kidney function and waste — blood urea nitrogen, creatinine; mineral — calcium; liver and protein, comprehensive panel only — albumin, total protein, alkaline phosphatase, alanine transaminase, aspartate aminotransferase, bilirubin.

The fishbone is bedside shorthand: position on the diagram identifies the test, so no label is written. Reynolds flagged what it leaves out — “this fishbone also includes the general normal ranges, but what it doesn’t have are the units … depending on where you practice will determine what the units are.”

5.2 · Where this deck disagrees with itself

Three reference ranges appear twice in the deck with different numbers — once on a teaching slide, once on the fishbone picture. Both are shown here rather than picking one, because she supplies ranges on the exam and no question can turn on the difference.

Reason to keep in view generally: a normal range is the mean plus or minus two standard deviations, so about 2.5 percent of healthy people fall outside it by chance — and a normal value does not exclude disease. Confirm a borderline abnormality before an extensive workup, and read every value against history, medications and supplements, alcohol and examination.

5.3 · Objective b(i–iv) — The electrolytes

Sodium is the major extracellular cation and its salts are the major determinant of extracellular osmolality. The serum level is a balance between oral intake and renal excretion. The single most useful idea in this lecture: an abnormal sodium is a water problem first — ask whether there is too much or too little free water before asking about salt. As free body water rises the sodium is diluted; the kidneys compensate by conserving sodium and excreting water. Serum sodium reflects water balance, controlled by thirst and antidiuretic hormone; total-body sodium, via the renin–angiotensin–aldosterone system, governs extracellular volume.

Potassium is the major intracellular cation and the key determinant of membrane electrical potential, especially in neuromuscular tissue. Small serum fluctuations carry large consequences, and both hyperkalemia and hypokalemia can cause life-threatening arrhythmias. It is excreted by the kidneys with no reabsorption, so it must be replaced by diet or supplementation or the level drops rapidly. Regulation is by aldosterone at the distal tubule and collecting duct, plus transcellular shifts driven by insulin, acid-base status and catecholamines — which is why the potassium in diabetic ketoacidosis can mislead.

Chloride is the major extracellular anion and follows sodium to maintain electrical neutrality. Alone it says little; with the other electrolytes it reports acid-base balance and hydration. It is reciprocal with bicarbonate: when carbon dioxide and hydrogen ions rise, bicarbonate moves out of the cell and chloride shifts back in. A low chloride with a high bicarbonate suggests metabolic alkalosis, classically from vomiting; the opposite pairing gives hyperchloremic non-gap acidosis.

Bicarbonate is the primary extracellular buffer and helps transport carbon dioxide. It is reported on the panel as “CO₂” — total carbon dioxide, which is mostly serum bicarbonate. Low means metabolic acidosis and is the trigger to calculate the anion gap; high means metabolic alkalosis.

5.4 · Objective b(v–vii) — Glucose, urea nitrogen and creatinine

Glucose is the body's main fuel, lowered by insulin and raised by glucagon and the counter-regulatory hormones, with a gluconeogenic contribution from the kidney. Always interpret it against the fasting or non-fasting state. Marked hyperglycemia lowers the measured sodium by dilution and drives osmolality.

Blood urea nitrogen is a nitrogenous waste product of protein metabolism, produced by the liver and cleared by the kidneys. It rises with reduced clearance but is non-specific — dehydration, gastrointestinal bleeding, high protein intake and catabolic states all raise it. Creatinine is a waste product of muscle creatine metabolism, filtered by the kidneys, and more specific. It rises as filtration falls, but is influenced by muscle mass, age and sex, so a normal creatinine can mask a reduced filtration rate in an elderly or cachectic patient.

Read the two together. A ratio above 20 to 1 suggests a prerenal cause; below that points to intrinsic renal disease. The estimated filtration rate is derived from creatinine — know of it, and do not calculate it.

5.5 · Objective c — The liver studies

Four patterns of hepatic abnormality:

Three shortcuts worth having: a ratio of aspartate aminotransferase to alanine transaminase above 2 to 1 suggests alcoholic liver disease; a raised aspartate aminotransferase without a raised alanine transaminase points to cardiac or skeletal muscle rather than liver; and transaminases in the thousands narrow to just three causes — viral, ischemia, toxins. Magnitude bands: mild under 5×, moderate 5–15×, severe over 15× the upper limit.

5.6 · Objectives d & e — Reading a panel, and the three patterns

Work through an abnormal comprehensive panel by organ system, in this order: electrolytes and acid-base (then calculate the anion gap) → renal, with the urea nitrogen to creatinine ratio → glucose → liver → minerals.

Two overlaps to know by name: hepatorenal syndrome shows liver and kidney failure together, and diabetic ketoacidosis produces electrolyte and renal derangements at once. Cardiorenal syndrome is the cardiac equivalent.

5.7 · Objective f — Electrolytes and acid-base, and the anion gap

These cannot be separated: they are regulated by the same renal transport mechanisms and physically coupled by electroneutrality.

• Potassium and pH. Acidosis drives potassium out of cells, raising the serum level; alkalosis drives it in, lowering it. Running the other way, potassium depletion increases renal acid secretion.
• Chloride. Losing it, as in vomiting, raises the strong ion difference and produces a metabolic alkalosis.

5.8 · Objectives g–i — Ordering, correlating, and fluid balance

Order a panel for: screening metabolic, liver and renal status; monitoring diabetes, chronic kidney disease, hypertension and liver disease; drugs with renal or hepatic toxicity or electrolyte effects; symptoms of fatigue, weakness, edema, jaundice, confusion, nausea and vomiting; acute illness with dehydration or a suspected acid-base disorder; and assessment of volume status.

Chemistry rarely stands alone. Abnormal liver tests → ultrasound first. A reduced filtration rate or albuminuria → urine studies and renal ultrasound; chronicity needs at least three months, and cystatin C confirms the rate when accuracy matters. Ketoacidosis → add ketones with beta-hydroxybutyrate, a venous blood gas, urinalysis, an electrocardiogram (for the potassium) and a complete blood count. Hyponatremia → add serum osmolality with urine sodium and osmolality.

5.9 · The vomiting case — why the two cannot be separated

A 25-year-old woman, three days of intractable nausea and vomiting. The panel shows low sodium, low potassium, low chloride, a raised bicarbonate and alkalemia.

Why it persists: volume, potassium and chloride depletion together force the kidney to reabsorb sodium and bicarbonate, which maintains the alkalosis after the vomiting has stopped. What fixes it: replacing sodium, chloride and potassium — saline with potassium chloride. Not bicarbonate, and not an antiemetic alone. Her speaker note calls this “the single best illustration that you cannot separate electrolytes from acid-base.”

6 · Urinalysis

6.1 · What the test is, and when to order it

Urinalysis examines the physical, chemical and microscopic contents of urine. It is inexpensive, non-invasive and fast, which is why it is done routinely on admission and in primary care, obstetrics and pediatrics alike. In a renal evaluation it complements the serum creatinine and blood urea nitrogen rather than replacing them.

It reaches well beyond the urinary tract: it speaks to hepatic and biliary disease, hydration status and infection. Any patient with abdominal, pelvic or back pain needs one.

6.2 · Inspection — color, transparency, odor

The examination starts the way a physical examination does, by looking.

The medication colors are a patient education point: tell the patient before they start, so a startling color does not alarm them.

Transparency runs clear → hazy → cloudy → turbid. Cloudiness comes from red cells, white cells, epithelial cells, bacteria, yeast, crystals, mucus, contrast media or fat. Foam is the one to notice separately — it points to protein.

Odor. Normal is called aromatic. An ammonia smell means the sample has stood long enough for bacteria to decompose its urea — refrigerate a specimen that will not be read within one to two hours, and add no preservative. A foul odor suggests bacterial infection; a fecal odor suggests an enterovesical fistula; a fruity or sweet odor means ketones, and sends you to the blood sugar.

6.3 · The reagent strip

A fresh specimen in a sterile container. Strips are kept desiccated. Results come in two shapes: qualitative (positive or negative) and semi-quantitative (trace, 1+, 2+, 3+ — a graded estimate, not a measurement).

Two practical traps. Reading time differs by analyte, so the strip cannot be read all at once. And manufacturers order the pads differently, so a strip must be read against its own chart — reading a pad against the wrong row is how the result goes wrong. An automated reader improves accuracy where one is available.

6.4 · pH, and what it does for stones

Urine pH reports the renal tubules' ability to hold the hydrogen ion concentration steady. The kidneys do that by excreting hydrogen ions as ammonium and by reabsorbing and producing bicarbonate. Four things move it: diet, medications, systemic acid-base disorders and tubular function.

Note the trap in the left column: renal tubular acidosis produces ALKALINE urine despite its name, because the defect is a failure to excrete acid.

6.5 · The two infection pads

Leukocyte esterase detects the esterase that white cells release. “Leukocyte esterase indicates pyuria. That’s the take-home point.” It rises with urinary tract infection, and also with interstitial cystitis and glomerulonephritis, both inflammatory rather than infective.

Nitrites. Urease-producing bacteria carry a reductase that turns urinary nitrates into nitrites. Two conditions have to be met for the pad to work: a urease-producing organism, and more than four hours of urine sitting in the bladder for the conversion. Sensitivity is about 50%, lower than leukocyte esterase.

6.6 · Ketones and glucose

Ketones are made in the liver from fatty acids and normally metabolized completely, so almost none reaches the urine. Ketonuria means cells are burning fatty acids rather than glucose — uncontrolled diabetes and ketoacidosis, starvation, fasting, alcoholic ketoacidosis, a high-fat low-carbohydrate diet, liver disease, and febrile illness in infants and children. Ketones on a strip should send you to the glucose.

Glucose is filtered freely and then wholly reabsorbed in the proximal tubules, so none should appear. It spills once the blood level exceeds the tubular threshold — around 180 milligrams per deciliter. Glucosuria is not diagnostic, because the threshold differs between people, but it always means further workup.

Three ways glucose appears without uncontrolled diabetes: impaired tubular reabsorption, so it spills at a normal blood level; dextrose-containing intravenous fluids; and pregnancy, where a trace is normal because the threshold falls.

6.7 · Objective b — blood, and the three things it can mean

This is the objective that carries its own bullet in the syllabus, and it turns on one fact: the pad detects heme, and heme sits in red cells, in free hemoglobin and in myoglobin alike. A positive result does not say which. What separates them is what else is true.

Gross hematuria is visible to the naked eye; microscopic hematuria needs analysis to find, and is defined as three or more red cells. A trace of blood can follow strenuous exercise in an otherwise well patient.

6.8 · Bilirubin and protein

Bilirubin. Only the conjugated form appears, because only it is water soluble. So bilirubinuria points to disease after conjugation — hepatic disease, or biliary obstruction such as a gallstone. Its screening value is timing: it can appear days before the patient looks jaundiced.

Protein — albumin, mostly — reports on glomerular and tubular function, and is reported semi-quantitatively. A trace can be normal in pregnancy, fever and strenuous exercise. Contamination with prostatic or vaginal secretions gives a false positive. Persistent proteinuria is a significant sign of renal disease, and a positive strip is followed by a twenty-four hour collection, which measures it properly rather than estimating.

Protein in the urine is not pathognomonic for anything — her words. It narrows the field; it does not name the disease.

6.9 · Specific gravity

The weight of the solutes in urine against an equal volume of water, which estimates the kidneys' concentrating and excretory ability. Water is 1.000, and urine can never quite reach it, because there is always some solute — hence a floor around 1.002.

It is affected by particle size, not just particle number. Her image: marbles dropped into a beaker weigh far more than the same volume of glitter. That is why radiographic contrast, whose particles are large, drives it above 1.040.

Insipidus means tasteless — the historical way of separating the two diabetes was to taste the urine. Sweet was mellitus; tasteless, and dilute, was insipidus.

6.10 · What comes after the strip

A microscopic urinalysis adds white cells, red cells, squamous epithelial cells, casts and crystals, and the specimen can go on for culture and sensitivity to name the organism and the agent that will treat it.

Bacteria are significant when the specimen came by straight catheterization, or when they sit alongside raised white cells and a positive leukocyte esterase. They are probably not significant when there are more than twenty squamous epithelial cells per high power field (contamination), or when they come from a longstanding indwelling catheter, which is colonized rather than acutely infected. Gram stain and culture are what make the diagnosis definitive.

6.11 · The worked case

A 28-year-old woman, two days of dysuria, frequency and urgency, mild suprapubic discomfort. No fever, no flank pain, no vaginal discharge. Temperature 37.0°C, blood pressure 112/68, heart rate 88, respiratory rate 16, oxygen saturation 99% on room air. Mild suprapubic tenderness, no costovertebral angle tenderness.

Next step: urinalysis. The dipstick came back positive for leukocyte esterase, nitrites and blood, and negative for glucose, bilirubin, ketones and protein.

Read it in two halves. The positives give pyuria, urease-producing bacteria and blood — the picture of a urinary tract infection. The negatives matter just as much: no glucose or ketones argues against a metabolic cause, no bilirubin against a hepatic one, and no protein against glomerular disease. Then send the culture and sensitivity.

Slide 36 is an unfinished answer slide — a dipstick chart carrying three unlabelled marks. Which analytes they sit against was resolved from their position on the chart, and matches what she read out. The recording stops mid-sentence at 49:41, part-way through her explanation, so the last few seconds of the class are not on tape.