How it's built

• This guide follows what Professor Burns covered in the Nov 10 live class (the transcript you sent). Each topic is filled in from the Chapter 7 (Neoplasia) and Chapter 8 (Blood and Clotting) slides and the Week 3 study guide PDF, then checked against the Tkacs textbook. Book page numbers are approximate (±1 page).
• ★ marks something the professor repeated, asked the class, or listed in his end-of-class “Remember…” review. Those are the most likely test items. He didn't promise any of them would be on the exam.
• ⚠️ marks something said in the lecture that the textbook or slides don't support, or that they contradict. Learn the textbook version for the exam. All of these are collected in the last section, “Lecture corrections & flags.”

Course notes from the lecture

• Discussions: the initial post is due by Wednesday, and your two replies are due by Sunday. Replies can go on any day, including the same day. An initial post plus 2 replies earns about 90–94%. Replying to more people (5–7) moves you toward 96–100%. Week 2 discussions were being graded Thursday and Friday, and you can still add to last week's.
• Syllabus: the course total was fixed from 110% to 100%. Discussion is worth 20%. The two APA competency exams are not graded.
• No Saturday lecture this week because the professor is on call. You can text or call him with questions.
• He said: “Please listen to my Kaiser Lives and look at the slides that I prepared multiple times, and you guys will do well.” He'll also post a board-prep slide deck that you will NOT be tested on.

Said in his end-of-class review

• ★ Rhabdomyosarcoma is a skeletal muscle tumor. Sarcomas come from mesenchymal tissue (Tkacs p. 222).
• ★ Xeroderma pigmentosum is a DNA-repair (nucleotide excision repair) defect, so UV damage can't be repaired. Patients must avoid sun and UV light and have a very high skin cancer risk (Tkacs p. 223).
• ★ EMT (epithelial–mesenchymal transition) lets cancer cells lose adhesion, become motile, invade, and metastasize (Ch 7 slide 19).
• ★ Most cancers come from sporadic mutations, usually environmental. Inherited cancer is uncommon (slides say <5%; the textbook says about 5–10%, Tkacs p. 227).
• ★ In older adults, check renal function before any cancer treatment because of tumor lysis syndrome risk (lecture; slides: “risk assessment guides treatment, hydration”).
• ★ G0 is the cell phase of cardiac myocytes and neurons: terminally differentiated, viable and functional, but not dividing (Tkacs p. 218).
• ★ An abnormal accumulation of cancer cells is a malignancy (tumor = abnormal mass of cells; malignant = invasive, poorly defined margins).
• ★ Telomerase rebuilds chromosome ends so cancer cells can keep dividing. This is “replicative immortality” (Tkacs p. 223).

Questions he asked the class (answers as the sources give them)

• ★ RBCs live 100–120 days and platelets 7–10 days. That's why a patient may need many platelet transfusions (lecture; Tkacs p. 242, 251).
• ★ High MCV with low hemoglobin: think alcohol use (lecture). Also think B12/folate deficiency, which is the textbook cause of macrocytic anemia (Tkacs p. 248–249). ⚠️ The alcohol link is a lecture point that isn't in the Tkacs chapter.
• ★ CKD anemia comes from loss of erythropoietin (EPO). Dialysis and renal patients get EPO injections (Tkacs p. 249–250).
• ★ Platelets dropping on heparin: order a HIT panel to check for heparin-induced thrombocytopenia (Tkacs p. 262, Box 8.2).
• ★ Best test to look for metastasis: a PET scan (Tkacs p. 226, 237). He said a bone scan is second if PET isn't affordable. ⚠️ The bone scan point isn't in the sources.
• ★ “Tricky board question”: is neuroblastoma treatable? He said yes, but not curable. His real point was to read whether the stem asks about TREATMENT or CURE. ⚠️ “Not curable” is contradicted: the textbook says about half of children diagnosed before 12 months have complete spontaneous regression (Tkacs p. 231).
• ★ Which antibiotic drops platelets? Linezolid (Zyvox) (lecture, Week 3 PDF). ⚠️ Not covered in Tkacs ch 8.
• ★ tPA vs urokinase: both convert plasminogen to plasmin, which breaks down fibrin (Tkacs p. 256–257). ⚠️ His claims that urokinase “works best” and isn't used in the U.S. because it's made from blood products aren't in the sources.
• ★ What does the body do first to limit bleeding? Vasoconstriction, the first stage of hemostasis (Ch 8 slide 31).

Key concepts

• Anemia is one of the most common disorders in the world and is mostly nutritional or genetic. In the U.S., iron-deficiency anemia prevalence is 5.6%: 10.4% of women, with Black women highest at 20.3% (Ch 8 slide 2; the lecture quoted the same numbers).
• Plasma is water, electrolytes, small molecules (O2, CO2, glucose, amino acids, fatty acids, metabolites), and proteins/lipoproteins. The formed elements are RBCs, WBCs, and platelets (Ch 8 slide 4).
• ★ Blood volume is about 7% of body weight, roughly 4.5–5.5 L in adults (the lecture said 4.5–5 L). Blood cells are about 45% of blood volume (Ch 8 slide 5).
• Blood's jobs: fill the circulation and help regulate BP, deliver O2 and nutrients, and carry wastes to the lungs, liver, and kidneys.
• RBCs carry O2 and CO2, platelets clot, and WBCs provide immune protection. ⚠️ The lecture said WBCs “come from your spleen.” Blood cells are made in the bone marrow, and the spleen clears and stores them.
• ★ RBCs (erythrocytes) make up 80% of the body's cells. They're biconcave disks about 7 µm across that squeeze through 5–6 µm capillaries. They have no nucleus or organelles, live 100–120 days, and most are cleared by splenic macrophages (Ch 8 slide 6; Tkacs p. 242).
• RBC production is driven by erythropoietin (EPO), cytokines, and colony-stimulating factors. Making RBCs takes lots of vitamin B12, folate, and iron (Ch 8 slide 8).
• Maturation: the nucleus is extruded to form a reticulocyte, which then loses its organelles to become a mature RBC (Ch 8 slide 9).
• Hemoglobin A has two α and two β chains, each with a heme. Each iron binds one O2. RBC hemoglobin is a supersaturated solution (31–36 g/dL) (Ch 8 slide 10).

Clinical pearl from lecture (trauma)

• If an actively bleeding trauma patient gets 4–5 L of saline, you've replaced their whole blood volume with crystalloid that doesn't carry oxygen. The professor said to start thinking about blood after about 2 L. ⚠️ The 2 L threshold is his clinical advice, not a textbook number. The blood volume numbers above are from the textbook.

Normal values (slides / Tkacs p. 242)

• Hematocrit (% of blood that is RBCs): men 39–54%, women 34–47%. The lecture rounded this to “about 40, 35 in women.”
• Hemoglobin: men 14–18 g/dL, women 11–16 g/dL. ⚠️ The lecture's “3-to-1 ratio” of hematocrit to hemoglobin isn't stated in the slides or chapter.
• MCV (mean cell volume = average RBC size): 80–100 fL. Below 80 is microcytic, 80–100 normocytic, above 100 macrocytic.
• RDW (red cell distribution width = variation in RBC size): 12–15%. It's high in sickle cell, hemolysis, and thalassemia (Tkacs p. 242).
• MCH: 27–33 pg. MCHC: 31–36 g/dL. Reticulocyte count: 0.4–1.8%.
• ⚠️ The lecture described the retic count as how “shaped and inflamed” cells are, and RDW as how big they “can get around.” The correct meanings: the reticulocyte count measures immature RBCs (it rises when the marrow is compensating, as in hemolysis), and RDW measures size variability.

Reading the smear

• Smear findings: microcytosis, normocytosis, macrocytosis, hypochromia (pale cells = low Hb concentration), and altered shapes like spherocytes, sickled cells, and schistocytes (RBC fragments) (Ch 8 slide 15).
• Order a peripheral smear when hemoglobin is low (lecture).

Sickle cell

• A missense mutation in the β-globin gene puts valine in place of glutamate at position 6, making HbS (Ch 8 slide 11; Tkacs p. 245).
• Heterozygotes have sickle cell trait and may be asymptomatic. Homozygotes have sickle cell disease with full manifestations.
• When deoxygenated, a hydrophobic “sticky” spot on HbS binds a pocket on the α chain. HbS polymerizes (nucleation) and the cell deforms into a crescent. Dehydration raises HbS concentration and can trigger a crisis (Ch 8 slides 11–13).
• Vaso-occlusion causes strokes, pain, acute chest syndrome, and renal failure. The spleen goes through repeated sequestration and atrophies, so infection risk is lifelong and immunizations matter (Ch 8 slide 71).
• There's no effect before birth because of HbF. Hemolysis starts after the switch to HbS, causing jaundice, splenomegaly, and anemia (Ch 8 slide 71).
• Lecture anecdotes: sickled cells get sticky, and he has seen MIs in 14-year-olds and strokes and ischemic limbs in adults. College athletes are screened for sickle cell. Patients do poorly in extreme cold or very dry heat. ⚠️ These are clinical stories that aren't in the textbook chapter.

Thalassemia

• Mutations of the β- or α-globin genes cause reduced or absent globin chain production (Ch 8 slides 14, 72).
• ★ Both α- and β-thalassemia make RBCs microcytic and hypochromic (small and pale) because of low hemoglobin concentration (Tkacs p. 245–246).
• α-thalassemia severity varies because there are 4 α-globin genes. Excess unpaired chains precipitate inside the RBC, damaging it and causing hemolysis. Iron overload can also occur.
• ⚠️ The lecture called thalassemias “your high RBC concentrations.” The slide's point is that RBCs normally hold a very high hemoglobin concentration, so an abnormal globin causes trouble. Thalassemia itself means reduced globin production, giving small, pale cells.

Iron handling

• Iron is needed to make hemoglobin and dissolves poorly, so it needs carrier proteins (Ch 8 slide 17).
• Ferritin is the intracellular iron-binding protein and short-term iron store. Some circulates in serum, so a serum ferritin level reflects stores.
• Transferrin is the plasma carrier that moves iron from the gut or spleen to the bone marrow.
• By the numbers: total body iron is 3–4 g. RBC production needs about 20 mg/day. The gut absorbs 1–2 mg/day and loses 1–2 mg/day. Normal transferrin saturation is 20–50% (Ch 8 slide 18).
• ★ 95% of the iron used for new RBCs is recycled from old RBCs broken down in the spleen. Only 5% is dietary, absorbed in the duodenum (Tkacs p. 246). ⚠️ The lecture said “most of your iron is stored in your spleen.” More precisely, most iron is recycled through the spleen, and the stores are in ferritin.

Iron-deficiency anemia (most common anemia worldwide)

• Causes: higher needs (pregnancy, early childhood, adolescence), chronic blood loss (menstrual or GI bleeding, often cancer-related), and low intake or absorption (poor diet, malabsorption such as IBD or celiac) (Ch 8 slide 20; lecture).
• It's a normal finding in infants and resolves once iron-containing foods are added. It's common in older adults and needs to be told apart from anemia of chronic inflammation.
• ★ Labs: MCV ↓ (microcytic, <80 fL), small pale (hypochromic) cells, transferrin/TIBC ↑, transferrin saturation ↓ (<20%), ferritin ↓, serum iron ↓ (Ch 8 slide 21; Tkacs p. 248).
• Symptoms: fatigue, weakness, dyspnea on exertion, pallor, and orthostatic lightheadedness (Tkacs p. 248). In children, also tachycardia, hair loss, and pica (Ch 8 slide 70).
• Bone marrow biopsy is the gold standard but is rarely done. Get a GI evaluation if occult blood loss or malabsorption is suspected (Tkacs p. 248).
• Clinical signs of anemia: acute blood loss brings hypotension (shock if severe), tachycardia, tachypnea, and syncope. Chronic loss brings slow-onset fatigue and exercise intolerance, with the kidneys retaining sodium and water to expand plasma volume (Ch 8 slide 16). The lecture's analogy was “adding more water to Kool-Aid.”

Vitamin B12 & folate

• Both are needed for nucleotide and DNA synthesis in dividing RBC precursors (Ch 8 slide 22).
• B12 comes from animal foods (meat, eggs, dairy), so vegans need supplements (lecture). Absorption needs intrinsic factor from gastric parietal cells, plus uptake in the ileum.
• Folate is in fruits, vegetables, legumes, and fortified cereals. Folate deficiency is less common because of widespread supplementation.
• B12 deficiency causes: malabsorption, bariatric surgery, and pernicious anemia (autoimmune destruction of parietal cells leading to no intrinsic factor) (Tkacs p. 248).
• ★ The anemia is macrocytic (MCV >100). Neutrophils are hypersegmented. Bone marrow shows megaloblasts, giant cells that haven't undergone mitosis (Ch 8 slide 23; Tkacs p. 249). (The slide also calls it “hypochromic,” but the textbook describes it only as macrocytic.)
• B12 is also needed for myelin, so deficiency causes neurologic deficits, especially sensory paresthesias. The anemia reverses with B12, but neuro deficits may not.
• ⚠️ The lecture said folate deficiency on a pirate ship causes scurvy. Scurvy is vitamin C deficiency, not folate.

Anemia of chronic inflammation (ACI)

• Chronic cytokine stimulation raises hepcidin, which blocks ferroportin, so iron is trapped in gut cells and splenic macrophages and can't reach the marrow (Ch 8 slide 24).
• The anemia is microcytic, like iron deficiency, with a low retic count, but ferritin is normal because total body iron is normal.

Anemia of chronic kidney disease

• ★ The main mechanism is loss of erythropoietin production, treated with EPO or its analogs (Tkacs p. 249–250). Iron deficiency, inflammation (hepcidin), and dialysis blood loss also contribute. Hemodialysis shortens RBC life span (Ch 8 slide 25).
• Lecture: most dialysis patients live with a hemoglobin of 7–8 and will never be 12–13. ⚠️ This is his clinical observation, not a textbook value.

Hemolysis

• Extravascular hemolysis means abnormal RBCs are destroyed by the spleen (e.g., sickle cell, hereditary spherocytosis, G6PD) (Ch 8 slide 26).
• Intravascular hemolysis includes microangiopathic causes, where clots in small vessels shred RBCs (HELLP, TTP, HUS), and autoimmune or drug-mediated causes, where antibodies and complement target RBCs.
• ★ Indicators: bilirubin ↑ (unconjugated/indirect), so jaundice; RBC count, Hb, and Hct ↓; reticulocytes ↑; RDW ↑; schistocytes; iron and LDH ↑ (Ch 8 slide 27; Tkacs p. 250). Splenomegaly, hepatomegaly, and gallstones can occur.
• Bilirubin pathway: RBC breakdown releases heme, which becomes biliverdin, then unconjugated bilirubin. The liver conjugates it and excretes it in bile (Ch 8 slide 28). The lecture point: “jaundice and hyperbilirubinemia go hand in hand” with hemolytic anemia.

G6PD deficiency

• In G6PD deficiency, RBCs can't make enough NADPH and reduced glutathione, so they're unprotected from oxidative stress (Tkacs p. 250).
• Triggers: oxidizing drugs (antimalarials, sulfonamides, nitrofurantoin) and fava beans. Hemolysis resolves once the exposure ends. Management is to avoid the triggers.
• ★ Lecture: check G6PD before starting an antimalarial (he named quinine for travel to Africa). ⚠️ He said the drug “will destroy all their platelets.” G6PD deficiency causes RED CELL hemolysis, not platelet destruction.

Stages of hemostasis ([S8] slide 31)

• ★ 1. Rapid vasoconstriction. 2. Platelets adhere, activate, and aggregate to form the primary platelet plug. 3. Coagulation proteins activate in sequence on platelet surfaces. 4. Fibrinogen is cleaved and fibrin stabilizes the clot. 5. The clot retracts after healing.
• Lecture pearl: a clean cut bleeds less than a tear, because a torn vessel can't retract cleanly. That's why degloving injuries bleed heavily. ⚠️ This is a clinical example, not in the slides.

Platelets

• ★ Platelets are fragments of bone marrow megakaryocytes. Thrombopoietin drives their production. They live 7–10 days and circulate between blood and spleen, where they're destroyed (Tkacs p. 251).
• Normal count is 150,000–450,000. Below 50,000 causes superficial bleeding (petechiae, purpura, ecchymoses) and gum bleeding, epistaxis, and menorrhagia (Ch 8 slides 56–57).
• Adhesion happens when exposed collagen binds vWF and platelets attach through glycoprotein Ib (GP Ib-IX-V). Aggregation happens through activated integrin GP IIb/IIIa binding fibrinogen (Tkacs p. 252).
• Lecture: if platelets suddenly drop (e.g., from 110 to 40–50), check glycoprotein Ib. ⚠️ GP Ib is the platelet adhesion receptor in the textbook, but it isn't presented as a routine first lab for a falling count.
• Healthy endothelium makes prostacyclin (PGI2) and nitric oxide, which keep platelets quiet. With injury, platelets make thromboxane A2 (TXA2), which drives activation, aggregation, and vasoconstriction (Ch 8 slides 36–37).
• Aspirin irreversibly blocks platelet COX-1, cutting TXA2 for the platelet's whole life span, which is why it's often stopped before surgery (Tkacs p. 252).

Cascade

• Most clotting proteins are made in the liver and circulate inactive. Proteases (XII, XI, X, IX, VII) activate one another, and thrombin (II) cleaves fibrinogen into fibrin (Ch 8 slide 38).
• Cofactors: tissue factor speeds VII, factor VIII speeds IX, and factor V speeds X.
• Extrinsic pathway: triggered by frank trauma, starts with tissue factor and factor VII. It's the fast one. Intrinsic pathway: triggered by stasis, starts with XII, and reinforces at factor IX. Common pathway: starts at factor X. Several steps need phospholipid and Ca2+ (Ch 8 slide 39).
• Liver carboxylation (vitamin K–dependent) lets clotting proteases bind calcium and stick to platelets. Warfarin blocks this step (Ch 8 slide 49).

Lab tests

• PT/INR: tissue factor is added, testing the extrinsic pathway. Used to monitor warfarin and liver disease (Ch 8 slide 40, 62).
• aPTT: tests the intrinsic pathway. Used for defects such as hemophilia A and B and to monitor unfractionated heparin (Ch 8 slide 41).
• D-dimer is a fibrin degradation product and a marker of thrombotic states (Tkacs p. 256–257).

Keeping clots in check

• Healthy endothelium makes NO and prostacyclin, proteoglycan (binds antithrombin), thrombomodulin (activates protein C), and tissue factor pathway inhibitor (Ch 8 slide 43).
• Antithrombin inactivates cascade proteases (heparin accelerates it). Protein C/S inhibits cofactors V and VIII (Ch 8 slides 42, 47).
• ★ Fibrinolysis: tissue-type (tPA) and urokinase-type (uPA) plasminogen activators turn plasminogen into plasmin, which breaks down cross-linked fibrin (Ch 8 slide 45; Tkacs p. 256). α2-antiplasmin and plasminogen activator inhibitor (PAI-1) restrain the system.

Drugs ([S8] slide 48)

• Acute MI or stroke: thrombectomy, tPA (fibrinolysis), clopidogrel and other platelet inhibitors, integrin inhibitors.
• Acute PE/DVT: heparin, an antithrombin accelerator.
• Chronic hypercoagulable states: aspirin, warfarin (blocks vitamin K carboxylation), and direct oral thrombin or factor Xa inhibitors.

Key concepts

• Virchow's triad: endothelial injury, venous stasis, and hypercoagulability (Tkacs p. 259).
• Arteries: endothelial injury and atherosclerotic plaque, so rupture causes rapid thrombosis (MI, stroke). Veins: slow flow and stasis. AFib also causes stasis and arterial emboli (Ch 8 slides 51–52).
• ★ DVT risk comes from immobility (“sedentary”), post-op status, and long plane or car rides. PEs usually come from a DVT, not from the lungs themselves (lecture; slides: clots break off and travel to the lungs).
• The most common population-wide cause of hypercoagulability is probably chronic inflammation. Cancer patients are also hypercoagulable (Tkacs p. 260; Ch 7 slide 21).

Factor V Leiden (hypercoagulable)

• ★ A missense mutation (arginine to glutamine) makes factor V resistant to activated protein C, which significantly raises the risk of VTE and PE (Ch 8 slide 53; Tkacs p. 260).
• ⚠️ The lecture said factor V Leiden “doesn't work here, that's why they bleed.” That's wrong: FVL causes CLOTTING (thrombosis), not bleeding.

Antiphospholipid syndrome

• An autoimmune hypercoagulable state, often with lupus. It can cause spontaneous abortion and is linked to preeclampsia and eclampsia. Suspect it when stroke or MI happens with no other risk factors (Ch 8 slide 54).

Thrombocytopenia & HIT

• Causes of low platelets: bone marrow failure (aplastic anemia, chemo, B12 deficiency), splenic sequestration or portal hypertension, and accelerated destruction (ITP, HIT) (Ch 8 slide 56).
• ITP: the post-infectious form is more common in children and resolves on its own. The autoimmune form is more common in adults and is treated with steroids or IVIG (Ch 8 slide 58).
• ★ HIT: IgG antibodies form against heparin bound to platelet factor 4. It occurs 5–10 days after heparin exposure. Platelets are destroyed and activated, so the danger is THROMBOSIS, not bleeding. Management: stop all heparin, use another anticoagulant, and generally avoid heparin for life (Tkacs p. 262, Box 8.2).
• ★ Lecture: in the ICU, if a patient on heparin becomes thrombocytopenic, order a HIT panel.

Von Willebrand disease

• ★ It's the most common inherited bleeding disorder (up to 2% of people, Tkacs p. 262). Type 1 accounts for 70% of cases and is autosomal dominant with incomplete penetrance (Ch 8 slide 59).
• Low vWF means poor platelet adhesion. Low factor VIII means IX works less well.
• Findings: mucosal bleeding, epistaxis, excessive childhood bruising, menorrhagia. Diagnosed with the ristocetin test.
• ⚠️ The lecture said “Von Willebrand is 70% common.” The 70% is type 1's share of vWD cases, not a prevalence.

Hemophilia A

• ★ Factor VIII deficiency, 4× more common than hemophilia B (factor IX). X-linked: a carrier mother can have an affected son or a carrier daughter, and an affected father can have a carrier daughter. 30% of cases are spontaneous mutations with no family history (Ch 8 slide 60; Tkacs p. 263).
• Severe cases cause hemarthroses (joint bleeds), hematomas, and intracranial bleeds, the leading cause of death. Labs: factor levels and a prolonged aPTT. Treatment: factor replacement (Ch 8 slide 61).
• ⚠️ The lecture said “you give them factor V.” Hemophilia A is treated by replacing factor VIII.
• Lecture history note: hemophilia A was “very rampant” in Europe in the 1600s–1800s. ⚠️ Not in the sources.

Liver disease

• The liver makes clotting factors and thrombopoietin. As liver disease progresses, PT rises. Portal hypertension sequesters platelets in the spleen. Without bile salts, vitamin K is poorly absorbed, so factors aren't carboxylated (Ch 8 slide 62).
• Lecture: in cirrhosis he sees INR 3–6 and platelets in the 40s. ⚠️ These are his clinical numbers, not textbook values.

Drugs that affect platelets (lecture)

• ★ Linezolid (Zyvox) can drop platelet and white counts significantly, so monitor them (lecture, Week 3 PDF). ⚠️ Not in Tkacs ch 7–8.

Key concepts ([S7] slides 2–4)

• Cancer is unregulated cell proliferation. It usually starts from one or a few DNA mutations caused by environmental exposures or random chance.
• Unregulated proliferation weakens DNA protections, so mutations keep accumulating (genetic instability). In many cancers, mutations allow invasion across the basement membrane and metastasis.
• ★ Proto-oncogenes code for growth proteins needed in embryonic development and childhood, then mostly shut off. A mutation can reactivate one into an oncogene (gain of function), driving repeated division that ignores normal limits (Ch 7 slide 15).
• ★ Tumor suppressor genes code for proteins that stop the cell cycle when DNA is abnormal (Rb, p53, p21, and DNA repair genes). Cancer needs loss of function in BOTH alleles.
• ★ Two-hit concept: with an inherited mutation in one allele, cancer doesn't develop until a second “hit” knocks out the other allele (Ch 7 slides 4, 23).
• Tumor genes are tracked during treatment to guide chemotherapy choices. The lecture example was sending a biopsy to a genomics lab to choose the best agent.

Phases

• Interphase covers G1, S, and G2. The commitment to divide controls the G1 to S transition. G2 checks DNA and cell contents before mitosis (Ch 7 slide 6).
• ★ G0 is a quiescent state where cells are viable and functional but not dividing. Mature cardiac myocytes and neurons sit permanently in G0. Senescent cells with critically short telomeres also enter permanent G0. Liver cells can re-enter the cycle and regrow (Tkacs p. 218–219).
• ★ Mitosis order: prophase, prometaphase, metaphase, anaphase, telophase, then cytokinesis (Tkacs p. 217).
• Prophase: chromatin condenses into chromosomes, kinetochores assemble at centromeres, and centrosomes move apart. The nuclear membrane is still intact.
• Prometaphase: the nuclear membrane breaks down and microtubules attach to kinetochores.
• Metaphase: sister chromatids line up at the center (the metaphase plate). The cell doesn't move on until every kinetochore is attached.
• Anaphase: the proteins linking the chromatids release, and shortening microtubules pull the sister chromatids to opposite poles. ⚠️ The lecture said chromatids “align” in anaphase. They SEPARATE in anaphase and align in metaphase.
• Telophase: kinetochores and microtubules disassemble and two nuclear membranes form. Cytokinesis then divides the cytoplasm (the cleavage furrow).

Control proteins ([S7] slides 10–12)

• Cyclins: their rising and falling levels move the cycle forward (pro-division). They're degraded after use.
• CDKs (cyclin-dependent kinases) are the workhorses and only work when their specific cyclin rises (pro-division).
• CKIs (CDK inhibitors) are activated by signals like p21 and halt CDK activity when there's a problem (anti-division).
• Cyclin D rises through G1. p53 (“guardian of the genome”) blocks progression if DNA is damaged. Cyclin E drives G1 to S. Cyclins A and B drive G2 into mitosis.
• Rb, p53, and p21 act mainly at G1 to S. They're tumor suppressors and are often mutated in cancer.
• ⚠️ The lecture said “checkpoint inhibitors” stop the cyclins, and that p21 “activates” CDKs. Per the slides, p21 activates CKIs, which HALT CDKs. In the textbook, “immune checkpoint inhibitors” are immunotherapy drugs (e.g., ipilimumab blocks CTLA-4) that boost the immune attack on tumors. They aren't cell-cycle blockers (Tkacs p. 235, 238).

Terms ([S7] slide 13)

• Tumor/neoplasm: an abnormal mass of cells.
• ★ Benign: grows slowly, well demarcated, doesn't infiltrate.
• ★ Dysplasia: abnormal-looking cells that can become malignant. Classic example: cervical dysplasia on a Pap smear, followed by colposcopy (lecture).
• ★ Carcinoma in situ: abnormal cells that stay within the basement membrane and are noninvasive.
• ★ Malignant: poorly defined margins and invasive.
• Blood cancers (“liquid tumors”) proliferate in the bone marrow and travel in the circulation with no solid tumor.

By tissue of origin ([S7] slide 14; Tkacs p. 222)

• Carcinoma means epithelial origin. Squamous cell comes from squamous epithelium, adenocarcinoma from GLANDULAR epithelium, and small cell carcinoma from neuroendocrine cells.
• Sarcoma means mesenchymal origin: bone (osteosarcoma), cartilage, smooth muscle (leiomyosarcoma), SKELETAL muscle (rhabdomyosarcoma), blood vessels (angiosarcoma), fat (liposarcoma).
• Hematopoietic cancers are leukemias and lymphomas. Melanoma comes from skin melanocytes. Teratomas come from germ cells.
• ⚠️ The lecture said adenocarcinoma is “usually from the gut” and squamous is “from the tissue.” The textbook definitions are glandular epithelium and squamous epithelium.

Hallmarks ([S7] slides 17–19; Tkacs p. 222–224)

• Uncontrolled proliferative signaling: oncogenes such as Ras (mutated in about 20% of cancers) and EGFR.
• Evading growth suppressors: loss of p53 and pRb.
• Genomic instability: failed DNA repair (e.g., xeroderma pigmentosum).
• ★ Replicative immortality: telomerase keeps rebuilding chromosome ends, so cells avoid senescence.
• Resisting cell death: cells ignore apoptotic signals. The lecture described this as cancer cells putting on “camouflage” to hide from macrophages.
• ★ Angiogenesis: growing tumors need a blood supply, so they make VEGF to grow new capillaries. Bevacizumab blocks VEGF (Tkacs p. 224). The transcript's “autogenesis” is a transcription error for angiogenesis.
• ★ Invasion and metastasis: through EMT, cells loosen their adhesion to the matrix, express matrix-degrading enzymes, and become motile.
• Evading immune destruction: tumors make immune-suppressive factors.
• Newer hallmarks: the microbiome, epigenetic reprogramming, and phenotypic plasticity.
• Tumor microenvironment: inflammatory signals. The deepest cells are hypoxic and acidotic, and stressed cells become more aggressive and invasive (Ch 7 slide 20).

Immune-based therapies

• ★ CAR-T: the patient's own T cells are engineered to attack their tumor. Checkpoint inhibitors let lymphocytes proliferate when stimulated (Ch 7 slide 19).
• ⚠️ The lecture's story about an AI-designed CAR-T drug given to its first human isn't in the sources. Treat it as a news anecdote, not test content.

Lecture claims to treat with caution

• ⚠️ “Pancreatic cancer is so aggressive because it taps the SMA, SMV, and portal vein.” “Sarcomas are among the slowest and worst tumors because of poor blood supply.” “Splenomegaly is common in cancer because dead cells overwhelm the spleen.” None of these are stated in the Ch 7 slides or chapter.

Systemic and local manifestations ([S7] slide 21; Tkacs p. 226)

• Inflammation and cytokines cause fever, malaise, and anorexia (suppressed appetite).
• Hypercoagulability raises thrombosis risk. Some patients first diagnosed with DVT/PE are later found to have cancer.
• Fatigue out of proportion to effort, and wasting.
• Endocrine effects: PTH-related protein causes hypercalcemia, and tumor-made vasopressin causes SIADH.
• Lecture: patients who lose 30–40 lb over about 3 months, or feel they've lost all their energy, need a workup.

★ Tumor lysis syndrome (memorize the labs)

• ★ Cause: starting chemotherapy kills many cells at once, and their contents flood the circulation (Tkacs p. 226; Ch 7 slide 22).
• ★ Labs: K+ ↑ (hyperkalemia), phosphate ↑, uric acid ↑, calcium ↓, and creatinine ↑ from acute kidney injury.
• It can cause acute renal failure. The lecture example: creatinine of 3–4 the night after a chemo round, needing a few dialysis runs.
• ★ Before chemo, risk assessment guides treatment and hydration. Check renal function first, especially in older adults.
• Lecture: talk with patients before treatment about side effects like bleeding disorders, possible dialysis, and sepsis risk.

Sporadic vs inherited

• ★ Sporadic mutations cause most cancers. Mutagens include smoking, UV light, older age, dietary factors, alcohol, obesity, and asbestos or other occupational exposures (Ch 7 slide 24). The lecture's examples were NASH/metabolic syndrome, alcohol and cirrhosis, rubber tire plants, and jet fuel on airport tarmacs.
• ★ Germline (inherited) mutations are present at birth, are a minority of cancers, usually involve tumor suppressor or DNA-repair genes, and usually need a second hit (Ch 7 slide 23).
• How common is inherited cancer? Slides: <5%. Textbook: “only about 5% to 10%” (Tkacs p. 226–227). The lecture said <5%.
• ⚠️ The lecture said BRCA is the “only one” high-risk inherited cancer. The slides also list Lynch syndrome and Li-Fraumeni syndrome.

Hereditary syndromes ([S7] slide 25; Tkacs p. 227)

• ★ Lynch syndrome (hereditary nonpolyposis colorectal cancer): defective mismatch-repair genes, linked to colorectal cancer.
• Li-Fraumeni syndrome: a TP53 mutation, so the cell cycle can't be halted. Causes early sarcomas, breast and brain cancers, and adrenal cortex tumors.
• ★ BRCA1/BRCA2: tumor suppressor/DNA-repair genes. Mutations raise the risk of breast, ovarian, fallopian tube, and prostate cancer (and male breast cancer).

Chromosomal changes ([S7] slide 26; Tkacs p. 227–228)

• B-cell (follicular) lymphoma: a translocation, usually t(14;18), activates the BCL-2 oncogene.
• ★ CML: the t(9;22) translocation forms the Philadelphia chromosome, creating the BCR-ABL fusion gene. Its tyrosine kinase is always on and drives unregulated division. Imatinib targets it (Ch 7 slide 28).
• ⚠️ The lecture said “with your BRCA gene you look for protein tyrosine kinase.” The tyrosine kinase is BCR-ABL in CML, not BRCA. HER2 (breast) is targeted by trastuzumab and lapatinib.

Cancer-causing viruses ([S7] slide 27; Tkacs p. 228)

• ★ Epstein–Barr virus is linked to Burkitt lymphoma (a B-cell lymphoma).
• ★ Hepatitis B and C are linked to hepatocellular carcinoma. The lecture added IV drug use and fatty liver as HCC routes.
• ★ HPV is linked to head and neck and anogenital cancers.
• Hep B and HPV have vaccines, so those cancers are preventable.

Diagnosis

• ★ PET scanning (FDG) exploits tumors' high glucose uptake to find tumors and metastases (Tkacs p. 226, 237).
• Isolated masses usually start with ultrasound. Suspected cancer of unknown origin gets CT of the chest and abdomen, then a biopsy (Tkacs p. 237).
• Oncology is becoming more individualized: tumor genotyping guides therapy, along with ablation and proton beam treatment (lecture; slides: genotyping leads to targeted therapy).

Pediatric ([S7] slide 29; Tkacs p. 231)

• The most common childhood cancers are leukemias and lymphomas, and the single most common is ALL.
• Childhood cancers favor nervous tissue (medulloblastoma, astrocytoma, neuroblastoma) and connective tissue (osteosarcoma, Ewing sarcoma). Wilms tumor (kidney) is embryonic. Retinoblastoma is genetic (RB1).
• Neuroblastoma: about half of infants diagnosed before 12 months have complete spontaneous regression. Children diagnosed later more often need treatment (Tkacs p. 231).

Older adults ([S7] slide 31; [S8] slides 73–76)

• Cancer risk rises with age: longer mutation exposure, weaker DNA repair, telomere shortening, less immune surveillance, and more senescent cells driving chronic inflammation.
• Adults 65+ are 15% of the U.S. population but 53% of cancer diagnoses (Tkacs p. 232).
• Blood: more anemia (iron more often than B12/folate, plus ACI and anemia of unknown origin), fewer marrow cells, a tendency toward hypercoagulability, and more anticoagulant use. The lecture noted elderly patients are often supplemented with folate, B12, B6, and magnesium.

Communication pearl (lecture)

• ★ Don't say “cancer” until a biopsy confirms it. Say “lesion,” “mass,” or “tumor,” because once patients hear “cancer,” they stop listening. Patients often worry about cancer and research it online (“Dr. Google,” ChatGPT). This is the professor's practice advice, not textbook content.

Contradicted by the textbook or slides (learn the book version)

• Factor V Leiden causes clotting (thrombosis), not bleeding (Tkacs p. 260).
• Hemophilia A is treated with factor VIII, not factor V (Tkacs p. 263).
• G6PD deficiency plus an oxidant drug (e.g., an antimalarial) causes RBC hemolysis, not platelet destruction (Tkacs p. 250).
• Scurvy is vitamin C deficiency, not folate.
• WBCs are made in the bone marrow, not “from your spleen.”
• Reticulocyte count measures immature RBCs, not cell shape or inflammation. RDW measures variation in RBC size.
• In anaphase, sister chromatids separate. They align in metaphase.
• p21 activates CKIs, which halt CDKs. It doesn't activate CDKs. Immune checkpoint inhibitors are immunotherapy drugs, not cyclin blockers.
• Inherited cancer isn't limited to BRCA: Lynch and Li-Fraumeni are also listed. The rate is <5% on the slides and about 5–10% in the textbook.
• The tyrosine kinase in CML is BCR-ABL, not linked to BRCA.
• “Neuroblastoma is not curable” is contradicted: many infants regress spontaneously (Tkacs p. 231). His actual exam tip was to read whether the question asks about treatment or cure.
• The 70% figure for vWD is type 1's share of vWD cases.
• Adenocarcinoma means glandular epithelium, not “from the gut.”

Said in the lecture but not in the textbook or slides (don't rely on these for exam answers)

• High MCV suggests alcoholism or gastritis. This is a common clinical association, but Tkacs ch 8 lists B12/folate deficiency as the macrocytic cause.
• Linezolid (Zyvox) lowers platelets and WBCs.
• Bone scan is second-line if PET isn't affordable.
• Urokinase is the “best” fibrinolytic and isn't used in the U.S. because it's made from blood products.
• Check glycoprotein Ib when platelets suddenly fall.
• Dialysis patients run Hb 7–8. Cirrhosis runs INR 3–6 with platelets in the 40s. Post-open-heart patients are run at Hb 7–8.
• Think about blood after about 2 L of crystalloid in trauma.
• Sickle cell stories: workers moved from Georgia to Arizona, and athlete screening.
• Pancreatic cancer and SMA/SMV, poor sarcoma blood supply, and splenomegaly from cancer cell breakdown.
• Hematocrit-to-hemoglobin “3 to 1” ratio.
• History and side stories (not test material): blood products in cosmetics, “blood roses,” hemophilia in Europe, Richard Branson's wife and PE, an AI-designed CAR-T drug, and the zombie/gene-editing joke. These couldn't be verified from your sources, so they're left out of the study content.

Note on the Week 3 PDF

• The Week 3 study guide PDF says “November 11, 2026,” but the transcript recording is dated Nov 10, 2026. The content matches the same lecture.