specific cancers and multiple system interactions

Question 1

What are the risk factors specific to breast cancer?

Answer 1

Ethnicity
Family History 
BRCA1 or BRCA2 (TS genes)
Benign Breast Growth
↑ Estrogen Exposure
Excessive Mammographies

Question 2

what are the harms of mammography?

Answer 2

False-Negatives & Positives
↑ Unnecessary Invasive Tx
↑ Radiation-induced BC (↑↑if < 30)

Question 3

where does most BC arise from?

Answer 3

Ductal Epithelium

Question 4

where are the common metastasis sites for breast cancer?

Answer 4

Lungs & Bones → Chest & Bone Pain

Question 5

what are the common manifestations of breast cancer?

Answer 5

Painless Breast Lump
Edema → Palpable Axillary LN
ECM Destruction → Nipple & Skin Retraction

Question 6

what are the specific risk factors for prostate cancer?

Answer 6

Old Age
Family History (BRCA deletions)
Race (Blacks)
Vasectomy → Debated
↑ Androgens Concentrations

Question 7

what are the harms of PSA screening?

Answer 7

High False-Negatives & Positives Rates
↑ Overtreatment
Biopsies related complications (ex.: infections)

Question 8

Age-Dependent ↓ Androgen Levels & 5α-reductase Activity
↓
High Estrogen : Low Testosterone Ratio → Prostate Inflammation
↓
Estrogen-Mediated ROS & DNA Toxicity → Precancerous Lesions (PIN)
↓
Repeated Cycles of Inflammation & Damage → Genetics/Epigenetics Alterations
↓
Carcinogenesis

Answer 8

Prostate cancer

Question 9

what are the common manifestation of prostate cancer?

Answer 9

Asymptomatic until Very Advanced
Progressive Urinary Obstruction
Large Tumor Growth → Constipation

Question 10

what are the common metastasis sites?

Answer 10

Lungs & Bones → Pain & ↑ Bone Fracture

Question 11

What do you call the respiratory tract epithelium cancer?

Answer 11

bronchogenic carcinoma

Question 12

what are the specific risk factors for lung cancer?

Answer 12

Cigarette Smoke by far!
Side stream Smoke
Asbestos & Coal Dusts

Question 13

rate those from slow to high rate:
 LCC
SCC
Oat Cell SCLC
Adenocarcinoma

Answer 13

SCC
Adenocarcinoma
LCC
Oat Cell SCLC

Question 14

match SCC, Adenocarcinoma, LCC, Oat Cell SCLC with their right association:
Strongest association with Smoking;
Neuroendocrine Cells → Frequent Paraneoplastic Syndrome
associated with smoking
Associated with Family History → EGFR mutations
Cells completely undifferentiated

Answer 14

SCC: associated with smoking
Adenocarcinoma: Associated with Family History → EGFR mutations
LCC: Cells completely undifferentiated
Oat Cell SCLC: Strongest association with Smoking;
Neuroendocrine Cells → Frequent Paraneoplastic Syndrome

Question 15

Environmental Carcinogens (ex.: Tobacco Smoke, Asbestos) → DNA Damage & Airway Injuries
↓
Carcinogenic ‘Hits’ Mutations & Inflammation → ROS & even more DNA Damage
↓
Repetitive Exposure to Harmful Carcinogens
↓
Metaplasia → Carcinoma In Situ → Invasive Lung Cancer → Metastasis

Answer 15

Lung cancer

Question 16

what are the specific manifestations for :
SCC
Adenocarcinoma 
LCC
oat cell carcinoma

Answer 16

SCC: Atelectasis & Airway Obstruction
Adenocarcinoma: Dyspnea & Pleural Pain
LCC: Airway Obstruction → Pneumonia
Oat Cell Carcinoma → Paraneoplastic Syndrome

Question 17

what are the common metastasis sites for lung cancer?

Answer 17

Brain, Liver & Bones → Mental Deficits, Bone Pain

Question 18

colorectal cancer:
what are the risk factors?
what is the cell type?

Answer 18

risk factors :
Polyps
Inflammatory Bowel Disease
Low Fiber/High Fat Diet

cell type: Adenocarcinoma

Question 19

Multistep Genetic Mutation Cascade:

1. Oncogene Activation (ex.: K-ras)
2. Tumor-Suppressor Gene Loss (ex.: APC, TP53)
3. Abnormal DNA Repair Mechanisms (ex.: EGFR)

Must Penetrate the Muscularis Layer to reach Lymphatics & Metastasise

Answer 19

Colorectal cancer

Question 20

What are the main metastasis sites for colorectal cancer?

Answer 20

Liver and lungs

Question 21

Benign Basal Cell Lesions
↑ with age
Hyperkeratotic scaly appearance
Chest, back & face

Answer 21

Seborrheic Keratosis

Question 22

Benign Squamous Cell Tumor
Arises from hair follicle
Dome-shpaed appearance
Resolves spontaneously

Answer 22

Keratocanthoma

Question 23

Premalignant Lesions → In situ SCC
Caused by prolonged UV radiations
Lesion is ‘felt’ more than seen
Prevent progression with clothing & sunblock

Answer 23

Actinic Keratosis

Question 24

Benign Melanocytic Lesions
Sizes and pigmentation varies
Can appear anywhere on skin
May transition into Melanoma

Answer 24

Nevi (moles)

Question 25

What is the main cause of cardiogenic shock?

Answer 25

Heart Failure:
Pump Failure → ex.: Myocardial Infarct (MI)
Insufficient Filling → ex.: Arrhytmias
Obstruction → ex.: Pulmonary Embolism (PE)

Question 26

↓ CO → ↓ O2 & Glucose Supply
                    ↓
Compensatory ↑ SNS & RAAS 
                    ↓
↑ O2 & Glucose Demand
                    ↓
↑ Burden on already weak/failing heart 
                   ↓
Vicious Cycle

Consequences : ↓ cardiac output, ↓ ejaculation fraction, persistent hypoperfusion and hypotension

Answer 26

Cardiogenic shock

Question 27

What is the main cause of hypovolemic shock?

Answer 27

Insufficient Vascular Volume ( >15% loss):
↓ Blood→ ex.: Hemorrhage
↓ Plasma → ex.: Burns
↓ Interstitial Fluid → ex.: Diuresis

Question 28

Compensatory ↑ SNS & RAAS 
                    ↓
Unable to compensate loss
                    ↓
↓ Tissue Perfusion
                    ↓
↓ O2 & Glucose Supply

Consequence: major decrease in CO

Answer 28

Hypovolemic shock

Question 29

What is the main cause of Neurogenic (Vasogenic) Shock ?

Answer 29

Insufficient Vascular Smooth Muscle Tone :

↓ Sympathetic Activity → Ex.: Spinal Cord Trauma; Depressive Drugs
↑ Parasympathetic Activity → Ex.: Medulla Injury

Question 30

Relative Hypovolemia’ → Unchanged Fluid Volume, but ↑ Space
              ↓
↓ Tissue Perfusion
              ↓
↓ O2 & Glucose Supply

Massive vasodilation

Answer 30

Neurogenic (Vasogenic) Shock

Question 31

What is the main cause of Anaphylactic Shock?

Answer 31

Hypersensitivity (Allergic) Reaction

Allergen ex.: Pollen; Drugs; Insects; Food

Question 32

IgE Anti-Allergen Abs Synthesis
                 ↓ 
Mast Cell Degranulation
                 ↓
Anaphylaxis = Massive Vasodilation & Systemic Inflammation
                 ↓
↓ Tissue Perfusion
                 ↓
↓ O2 & Glucose Supply

*hypovolemia

Answer 32

Anaphylactic Shock

Question 33

Systemic Inflammatory Response Syndrome (SIRS)
               ↓
Sepsis (SIRS + MODS)
               ↓
Septic Shock (Constant Hypotension)

Answer 33

Septic shock

Question 34

general pathology for MODS

Answer 34

Initial Injury → Primary MODS
                      ↓
Leukocyte Priming → Mild Second Injury
                       ↓
 Disproportionate Response → Secondary MODS

Question 35

Pathophysiologic hallmarks for MODS

Answer 35

Blood Flow Maldistribution → Organ Hypoperfusion

Hypermetabolism → Extreme Protein Catabolism

Question 36

What are the consequences of MODS?

Answer 36

Supply-Dependent O2 Consumption → Tissue Hypoxia

Reperfusion Injury

Question 37

Hypovolemic Shock + Cellular/Immune Disruption

Myocardial Depression → ↓ Tissue Perfusion
↓
↓ Visceral Organ Functions

Compensatory ↓ Urine Output

Answer 37

Burn Shock

Question 38

What are the cinical manifestations of burn?

Answer 38

Massive Edema

↑↑↑ Evaporative Water Loss

Altered Cell Membrane Permeability

Question 39

Which of the following ‘Type of Shock – Potential Cause’ pairs is correctly matched?
A. Bee Sting – Septic Shock
B. Pulmonary Edema – Hypovolemic Shock
C. Burn – Cardiogeneic Shock
D. Depressant Sleeping Pills – Neurogenic Shock

Answer 39

D.