LEap D Part 3

Breast Cancer

100

 Describe mutations associated with breast cancer.

Atypia increase risk for cancer and include ADH and ALH (lacks E cadherins). Without atypia include epithelial hyperplasia, sclerosing adenosis, intraductal papilloma, complex sclerosing lesion. (look at notebook for picture references)

200

Describe the benign stromal tumors of breast and treatment.

Fibroadenoma - solid well defined. Low cellularity. Phyllodes tumor - stromal outgrowth - leaf like in nodules. Treat both by removing or observe.

300

Describe mutations associated with breast cancer.

BRCA 1/2 - tumor suppressor, incomplete penetrance, autosomal dominant. TP53 - tumor suppressor with complete penetrance. PI3K-AKT - pro growth and activated when mutations lead to HER2 overexpression, oncogene PI3K and tumor suppressor PTEN

400

What are risk factors and protective factors for breast cancer?

Risk - mutations, fhx, estrogen, alcohol, age. Protective - obesity, exercise, early pregnancy, lactation, aromatase inhibitors

500

Distinguish invasive ductal vs invasive lobular breast cancer.

Ductal - cells in milk ducts, most breast cancer, ER +, firm, hard, with sharp margins, outer breast quadrant, related to DCIS. Lobular - cells in the glands, loss of E-cadherin ordered in single file, skin dimpling, difficult to image, NOT related to LCIS, mets to CSF

Hepatitis

100

Describe the symptoms, labs, imaging and treatment of alcoholic hepatitis and differeniate between alcoholic steatosis

• Alcoholic steatosis
•  
  • Occurs first 
  •  
  • Can progress to alcoholic      hepatitis
  •  
  • Treatment
  •  
    • abstinence
•  
• Alcoholic hepatitis
•  
  • Acute severe inflammation      with liver failure
  •  
  • High short term mortality
  •  
  • Can lead to cirrhosis
  •  
  • Symptoms
  •  
    • Fatigue
    •   
    • RUQ
    •   
    • Anorexia
    •   
    • Jaudnice
    •   
    • Fever
    •   
    • Tender hepatomegaly
  •  
  • Labs
  •  
    • Elevated ALT and AST but       less than 300
    •   
    • AST is higher than ALT
    •   
    • GGT is induced by alcohol,       usually markedly elevated
    •   
    • Alk phos- hepatobiliary       origin- elevated
    •   
    • Elevated bili- detected in       urine --> conjugated hyperbilirubinemia
  •  
  • Imaging
  •  
    • US, hetergenous, bright-       hyperechoic
    •   
    • CT- darker than the spleen-       hypoechoice
    •   
    • Histology
    •   
      • Mallory bodies- depositis        of hyaline in the hepatocytes
  •  
  • Treatment
  •  
    • Abstinence
    •   
    • High calorie high protein       diet
    •   
    • Give steroids if they have       no infection currently

200

Describe the epidemiology of NADFLD, the disease progression, the symptoms, imaging and treatment

• Almost always occurs with insulin resistant and in obese people
• Not due to alcohol
• Steatosis--> steatohepatitis--> inflammation --> fibrosis --> cirrhosis
• Steatosis
• 
  
  • Not inflammatory
  • Is reversible
  • Increase TG stores in hepatocytes
  • No change in ALT and AST
• Steatohepatitis
• 
  
  • Inflammatory changes in addition to TG deposits
  • Is reversible
  • Has a 10-15 change of developing into cirrhosis
  • Elevated ALT and AST
  • Alk phos MAY be elevated as a marker of cholestasis
  • 
    
    • Swelling and compression of the bile ducts due to swollen heaptic ducts
  • Mallory hyaline
  • Focal hepatocyte necrosis
  • Lobar inflammation and fibrosis
• Symptoms
• 
  
  • Usually asymptomatic
  • RUQ pain
• Imaging
• 
  
  • US- hetergenous- bright
  • CT- hypoechoic in comparison to the liver
  • Fibroscan
  • 
    
    • Distinguish between cirrhosis and no cirrhosis
  • Liver biopsy
  • 
    
    • Distinguish between steatosis and NASH

300

Differentiate between primary and secondary hemochromatosis

Primary hemochromatosis

• C282Y Mutation in HFE so it cant work with transferrin 2 to increase hepcidin
• Unable to activate hepcidin--> unable to stimulate enterocytes to internalize their ferroportin channels--> high iron--> taken into cells
• Iron can be toxic--generates ROS
• Treatment
• 
  
  • Phlebotomy
  • Liver transplant--> only for liver failure or liver cancer

Secondary hemochromatosis

• Due to hypoxia
• Could be due to anemia
• hypoxia downregulates hepcidin
• No hepcidin--> increase in iron levels--> taken into cells
• Iron can be toxin- generates ROS
•  blood transfusions make the problem worse
• Treatment
• 
  
  • Cant do phlebotomy
  • Have to do chelation

400

Symptoms of someone with hemochromatosis

• Weakness
•  
  • If anemic
•  
• Arthritis
•  
  • Proliferation of the      synovium--> fibrosis and calcifications
•  
• Diabetes
•  
  • Iron deposits in the      pancreatic islet cells and loss of insulin
•  
• Loss of libido and impotence
•  
  • Anterior pituitary-->      decreased gonadotropin production --> testicular atrophy and      amenorrhea
•  
• Cardiac failure
•  
  • Iron deposits in the heart      --> myopathy --> heart failure
  •  
  • Arrhythmias are the most      common cause of death
•  
• Hyperpigmentation
•  
  • Iron deposits in the skin      -> tan skin
•  
• Ascites
•  
  • Due to cirrhosis
•  
• Hepatomegaly

500

Symptoms of someone with cirrhosis and what caused them

• Ascites
•  
  • Increased hydrostatic      pressure in the sinusoids--> fluid moves into the lymphatics -->      increased pressure in lymphatics --> fluid leaks into the peritoneum      producing ascites
  •  
  • Effective blood volume      decreases--> increase in mineralocortioids--> retain salt and water
•  
• Bleeding
•  
  • No clotting factors being      made
  •  
  • No thrombopoetin production      for platelet formation
•  
• Portal hypertension
•  
  • Cirrhosis and decreased      compliance of the sinusoids in the liver--> congestion
  •  
  • Hepatocytes are unable to      access blood due to fibrosis
  •  
  • Blood diverts to low      pressure areas
•  
• Caput medusa
•  
  • The back flow of blood into      the umbilical vein
•  
• Esophageal varices
•  
  • Portal hypertension
•  
• Hemorrhoids
•  
  • Portal hypertension
•  
• Estrogen
•  
  • High because liver is no      inactivating it
  •  
  • Palmar erythema
  •  
  • Spider angiomas
  •  
  • gynecomastia
•  
• Splenomegaly
•  
  • Due to increase compensatory      NO as a result of the splenic hypertension
•  
• Hepatic encephalopathy
•  
  • Increase build up of toxic      endogenous substances
  •  
  • Build up of ammonia from      bacteria in the gut 
•  
• Shunting
•  
  • Decrease in portal flow      results in shunting to low pressure areas
•  
• Jaundice
•  
  • Build up of bilirubin

Lung

100

Explain the major differences between a restrictive and obstructive disease. Include PFT test values, what they look like in a graph, and examples of each

1. Normal or Inc FEV1/FVC ratio,     dec FVC, dec FEV1
2.  
3. Dec FEV1/FVC ratio, dec FVC,     dec FEV1

200

What is the pathophysiology of cor pulmonale? What symptoms can you see? 

1. Pulmonary hypertension -->     increased RV afterload --> RV hypertrophy --> RV failure
2.  
3. Dyspnea, lower extremity     edema, ascites 

300

What is the pathophysiology of COPD and what diseases does it include? What is the clinical presentation? What are key findings in imaging? 

1. Pathophysiology: airflow is     obstructed, so it is hard to get air out. This leads to air trapping     (increase in residual volume). The air trapping leads to progressive     hyperinflation of the lung 
2.  
3. Clinical presentation: cough,     sputum production, exertional dyspnea, wheezing, crackles, clubbing,     barrel chest
4.  
5. Imaging: barrel chest; can     see lung hyperinflation as well 

400

What is the pathophysiology of idiopathic pulmonary fibrosis and what is the clinical presentation? What are key findings in imaging? 

1. Pathophysiology: lung injury     --> inflammatory cell influx -- leading to:
2.  
   1. Endothelial cell      damage --> coagulation cascade activation via endothelin 1      (vasoconstrictor)
   2.  
   3. Damage/destruction to      alveolar epithelium --> release of cytokines, chemokines, growth      factors (TGF-beta, CTGF, IGF-1) 
   4.  
   5. These two things lead to      activation of fibroblasts --> pulmonary fibrosis --> deposition of      collagen in lung parenchyma
3.  
4. Clinical Presentation:     bibasilar crackles, clubbing of fingers 
5.  
6. Imaging: honeycombing in     chest CT; increase in reticular opacities on chest x-ray
7.  
8. Histo: fibroblast foci,     interstitial inflammation 

500

Describe the concept of equal pressure point. What happens to the equal pressure point in diseased lungs? 

1. Airway pressure in alveoli =     pleural pressure
2.  
3. Normal lungs, EPP should be     in the reached in the cartilage because this would prevent collapse of     airways. 
4.  
5. Diseased lungs, EPP moves     towards the alveoli which compresses the airways. 

Hematuria

100

Describe the process of micturition from bladder filling to voiding. 

I'm not typing an answer to this lol put the screenshot from the notebook pls.

200

What types of pathology can effect micturition and how?

MS, UMN lesion and UTI cause urge incontinence. LMN and DM (overflow incontinence)

300

Describe acute and chronic effects of obstructive uropathy/nephropathy.

Acute - dec GFR and inc NA reabsorption leading to hypernatremia and azotemia so BUN/Cr is high - little urine. Chronic - hypervolemia triggers ANP and BNP - downreg of RAAS so loss of medullary hypertonicity and kidney loses concentrating ability so get polyuria and nocturia. Dec ENaC also dec efflus of K so can get hyperkalemia. Can lead to RTA. 

400

Describe process of post-obstructive diuresis. 

Removal of obstruction causes massive polyuria and can lead to overcorrection resulting in hypovolemia or hypotension so treat with fluids.

500

List     surgical and nonsurgical treatments for obstructive uropathy. 

Lithrotripsy, stent, nephrostomy, catheter, alpha block, alpha reductase, fluid, and abx

SLE

100

What is the common presentation of SLE?

see pic

200

What DNA antibodies are associated with SLE?

ANAs

• Anti-double-stranded-DNA antibody (anti-dsDNA):
• 
  
  • Is a type of ANA antigen and is specific to SLE. -do not use to track disease
  • Titers of anti-dsDNA vary over time ---> tends to increase with flares
  • Associated with renal involvement ---> glomerulonephritis
  • However, absence of anti-dsDNA does not exclude a diagnosis of lupus.
• Anti-Smith (anti-Sm):
• 
  
  • Specific for SLE ---> MOST SPECIFIC
  • Directed against small nuclear ribonucleoproteins (snRNPs)
• Anti-SS-A (Ro nucleoprotein):
• 
  
  • Associated with neonatal lupus and congenital heart block

300

What stages of lupus nephritis is associated with nephrotic? Nephritic?

Classification

Considerations

Class 3 Focal Lupus Nephritis

 

Class 4 Diffuse Proliferative Lupus Nephritis

Class 5 Membranous Lupus Nephritis

400

What are treatment options for SLE and there MOA?

Anti-inflammatory drugs: Inhibit COX2 and have been claimed to promote death of autoreactive T cells

• NSAIDS

Antimalarial Agents: inhibits the function of toll-like receptors that contribute to autoimmunity

• Hydroxychloroquine:  patients with SLE of any type should be treated with hydroxychloroquine
• chloroquine, and quinacrine

Immunosuppressive Agents:

• Cyclophosphamide- alkylating agent
• Methotrexate- a folic acid antagonist
• Azathioprine- a purine analogue and cycle-specific antimetabolite
• Mycophenolate mofetil- a relatively lymphocyte-specific inhibitor of purine synthesis

Glucocorticoids (prednisone): suppress immune system

Monoclonal Antibodies: antibody against IL-6. inhibit C5, block CD20

500

What is Rituximab used for and what is its MOA?

Rituximab

• 
  
  • Monoclonal antibody        directed against CD20 antigen on B cells
  •    
  • Binds antigen and induces        complement-dependent B cell cytotoxicity

Lupus nephritis  life threatening