Pathophysiology, final test

test on friday

Gastroesophageal Reflux disease (GERD)

Stomach contents flow back into the esophagus 

LES (lower esophageal sphincter) is weak

Whiteboard example for GERD:

shows a stomach on the board and the LES flap and the stomach has acid in it, and it shows the LES flap allowing acid into the esophagus which causes the heart burn and or can be causes by chronic coughing if i remember right

Gastroesophageal reflux disease (GERD)

Complications 

Esophagilits 

Ulcers and bleeding 

Strictures 

Barretts esophagus 

Risk factors: GERD

Decrease LES tone 

Meds 

Hiatal hernia 

Increase abdominal pressure 

1 obesity 

2 pregnacy 

3 coughing 

4 heavy lifting

Triggers: GERD

Alcohol

Tabacco 

Caffeine 

Spicy food

Rheumatoid Arthritis 

Chronic 

Autoimmune disease 

Causes joint destruction (progressive)

Can also effect : 

1 skin 

2 lungs 

3 BV’s (blood vessels)

Patho: for Rheumatoid arthritis: full definition

Trigger→ Altered proteins→ immune activation→ inflation pannus → joint destruction→systemic effects 

WE are now going more indebted to each one down below

Patho: for Rheumatoid arthritis: step 1-3

Trigger→ Altered proteins→ immune activation→

Patho: for Rheumatoid arthritis: step 4-6

inflation pannus → joint destruction→systemic effects

RA (Rheumatoid Arthritis) Triggers

Triggers:

Requires genetic predisposition (Genetic triggers)

(HLA-DR4.HLA-DR1)

Requires an environmental component (triggers)

Smoking 

Infection 

Genetics+ environmental factors= abnormal immune response

Protein changes: RA (Rheumatoid Arthritis)

Self proteins become altered 

Citrillunation 

Body (immune system) now see theses proteins as foreign  

Whiteboard example of how the protein changes in RA:

 the protein changes in a way that the body does not requnize it, it comes in MR. Brady house with a mask on he doesent requnize them

Immune activation: RA (Rheumatoid Arthritis)

Antigen-presenting cells 

Activation T cells 

T cells activate B cells 

All of this lead to inflammatory cytokines and antibodies

*** Production of autoantibodies: RA (Rheumatoid Arthritis)

B cells→ plasma cells→ autobodies 

Rheumatoid Factor (RF)

Anti-CCP( they are the immune system Making antibodies on their own proteins)

Theses all causes immune complexes in joints

Joint inflammation: RA (Rheumatoid Arthritis)

Mediated by immune cells and cytokines 

Swelling,Pain,and recruitment of more immune cells

Pannus formation: RA (Rheumatoid Arthritis)

When the synovial membrane Becomes: 

1 thick 

2 inflamed 

3 overgrown 

Joint destruction: RA (Rheumatoid Arthritis)

Pannus leads to: 

Cartilage breakdown

Bone erosion 

  Activated osteoclasts 

Joint deformity 

Loss of function 

Systemic effects: full definition: RA (Rheumatoid Arthritis)

Cytokines enter the blood! 

Medical symptoms:

Fatigue 

Fever 

Anemia 

Skin 

Lungs 

And other organs are affected 

Symmetrical affected (so both sides are affected)

Greater than or equal to 5 joints affected 

Most common is joints of the hands and feet 

Symptoms:

Pain swelling or warmth

Morning stiffness 

Exercise benefits: 

Arthritis gets worse without exercise 

Exercise helps with inflammation as well

Medical symptoms, and Symptoms: RA (Rheumatoid Arthritis)

Medical symptoms:

Fatigue 

Fever 

Anemia 

Skin 

Lungs 

And other organs are affected 

Symmetrical affected (so both sides are affected)

Greater than or equal to 5 joints affected 

Most common is joints of the hands and feet 

Symptoms:

Pain swelling or warmth

Morning stiffness 

Exercise benefits: With RA (Rheumatoid Arthritis)

Arthritis gets worse without exercise 

Exercise helps with inflammation as well 

Deformities of RA (Rheumatoid Arthritis): full definition

Ulnar deviation 

Boutonniere deformity 

Swan neck deformities
Other finding:

Bakers cyst 

Rymutoid nodules on the elbows 

Scaring of the lungs, due to inflammation

Other finding: Deformities of RA (Rheumatoid Arthritis)

Bakers cyst 

Rymutoid nodules on the elbows 

Scaring of the lungs, due to inflammation

Systemic Lupus Erythematosus(SLE): full definition

Affects multiple organs ( especially the skin 

Autoimmune disease 

Affects women more than men 

Genetics+ environmental factors 

Patho: of Type 3 hypersensitivity reaction Systemic Lupus Erythematosus (SLE)

Environmental trigger → cell damage→Genetic susceptibility→Immune recognition error→ immune complex formation→ tissue deposition and damage

Systemic Lupus Erythematosus(SLE): Main definition

Affects multiple organs ( especially the skin 

Autoimmune disease 

Affects women more than men 

Genetics+ environmental factors

Patho: of Type 3 hypersensitivity reaction Systemic Lupus Erythematosus (SLE)

Environmental trigger → cell damage→Genetic susceptibility→Immune recognition error→ immune complex formation→ tissue deposition and damage

Patho: of Type 3 hypersensitivity reaction Systemic Lupus Erythematosus (SLE): step 1-3

Environmental trigger → cell damage→Genetic susceptibility→

Patho: of Type 3 hypersensitivity reaction Systemic Lupus Erythematosus (SLE): step 4-6

Immune recognition error→ immune complex formation→ tissue deposition and damage

Environmental trigger: type 3 Systemic Lupus Erythematosus(SLE)

Uv light 

Smoking 

Infections 

Certain drugs 

estrogens*

Cell damage: type 3 Systemic Lupus Erythematosus(SLE)

Damage to dna 

Leads to apoptosis 

Exposure of intracellular material

Genetic susceptibility: type 3 Systemic Lupus Erythematosus(SLE)

Genes reduce clearance of Apoptotic cells 

Nuclear material stays around longer than needed!

Immune recognition error: Type 3 Systemic Lupus Erythematosus(SLE)

Immune system recognizes nuclear material as foreign 

B cells produce nuclear antibodies

Tissue deposition and damage: Type 3 Systemic Lupus Erythematosus(SLE)

Kidneys

Skin 

Joints 

Heart 

Activation of complement system 

This leads to inflammation and tissue damage

*antibodies also attack: Type 3 Systemic Lupus Erythematosus(SLE)

RBCs

WBCs

Platelets

Phospolipids

Symptoms and signs: full definition: of Type 3 Hypersensitivity reaction Systemic Lupus Erythematosus(SLE)

SLE immune system attacks organs and you immune system attacks itself

Malar rash

Is a butterfly rash upon the cheeks of your face 

Discoid rask 

Scaring and plaque like lesion on the skin   

Photosensitivity 

Rash due to UV light 

Oral or nasal ulcers 

Serosal inflammation 

Affects the serious membrane EX the membranes that surrounds the heart and lungs leading to carditus and pericarditis  

Kidney damage 

Inflammation 

Start peeing out proteins 

Psychosis 

Seisures 

Anemia (destroying the red blood cells)

Low platelet cells

Symptoms and signs: Main definition: of Type 3 Hypersensitivity reaction Systemic Lupus Erythematosus(SLE)

SLE immune system attacks organs and you immune system attacks itself

Malar rash: of Type 3 Hypersensitivity reaction Systemic Lupus Erythematosus(SLE)

Is a butterfly rash upon the cheeks of your face

Discoid rash: of Type 3 Hypersensitivity reaction Systemic Lupus Erythematosus(SLE)

Scaring and plaque like lesion on the skin

Photosensitivity: of Type 3 Hypersensitivity reaction Systemic Lupus Erythematosus(SLE)

Rash due to UV light

Serosal inflammation: of Type 3 Hypersensitivity reaction Systemic Lupus Erythematosus(SLE)

Affects the serious membrane EX the membranes that surrounds the heart and lungs leading to carditus and pericarditis

other symptom’s: of Type 3 Hypersensitivity reaction Systemic Lupus Erythematosus(SLE)

Oral or nasal ulcers 
Kidney damage 

Inflammation 

Start peeing out proteins 

Psychosis 

Seisures 

Anemia (destroying the red blood cells)

Low platelet cells

Skin cancer

Very common 

1-5 develop it (but brady roles his eyes at it)

Develop light through exposure to UV light 

Depends on whos the doctors on the amount of later to apply 

When diagnosed highly treatable 

UV light leads to damaged DNA

Symptoms: Skin cancer

Common injury to DNA is Pyrimidine Dimer(mutation)

DNA sticking together improperly

It can correct most of them but it doesn't fix all of them

Patho: Skin cancer

Mutations built up in the gene so when the cell divides it copies its self normally But someone with a mutated cell Gives rise to a ton of cells Because the gene thats is supposed to control proliferation is mutated 

UV light→leads to failed system repair→mutations of Gene that controls replication

Patho: Skin cancer: push arrow

UV light→leads to failed system repair→mutations of Gene that controls replication

Genetics: Skin cancer

Melin controls UV Radiation its the body natural sunscreen 

Melin produces melianocytes which helps protect from UV radiation 

Albion gotta be carefull for they dont have melin 

Range from slow and local to fast and deadly

Whiteboard example of skin cancer

showed a human going outside and the sun is applied to his skin and too much sun exposure leads to damaged DNA. UV light leads to damaged DNA

Basal cell carcinoma (BCC)

Found in the Basale layer 

Most common 

Pearly,shinny bump 

Pink color 

May crust or ulcerate 

Grows slow 

RARELY spreads 

Can invade locally if Ignored 

Low mortality rate

Squamous cell carcinoma (SCC)

Stratum Spinosum layer of the Epidermis 

Mildly aggressive (middle ground)

Usually starts as Actinic Keratosis 

Rough,  scally, lesion precancer 

Then bowen disease→cancer in place 

Cancer in place not invading yet 

Then invasive SCC→ breaks into deeper tissues!

Red,scaly,lesion 

May ulcerate 

Shows up in sun exposed areas 

Often in hands 

But shows up in areas like face necks hands and ears 

Can metastasize 

“Keratin pearls” are a pathology clue

Patho clue for Squamous cell carcinoma (SCC)

“Keratin pearls”

Keratoacanthoma

SCC(squamous cell Carcinoma) look a like 

Grows rapidly (domeshaped)

Central Keratin-filled crater

Melanoma “Dangerous one”: full definition

Origin 

Melanocytes 

Produce melanin (Skin color, hair color natural sunscreen etc)

Metastasize

Leading cause of death 

Develops:

Growth sideways 

Goes from time circle to medium circle to big circle with jaggy edges 

Grow downwards (vertical phase)

Invades deeper skin 

Ugly change mole 

There is no symmetry

Can have different Colors 

Once you find one and cut it out your more prone to get another one

how does it Develops: Melanoma

Growth sideways 

Goes from time circle to medium circle to big circle with jaggy edges 

Grow downwards (vertical phase)

Invades deeper skin 

Ugly change mole 

There is no symmetry

Can have different Colors 

Once you find one and cut it out your more prone to get another one

Whiteboard example of mole spreading through the epidermis layer to the dermis layer:

 if the mole stays in the epidermis that great because it has no accuse to blood cells, but if it spreads to the dermis then it gets access to blood cells and then that's bad and you need to get a CT 

ABCDE

Asymmetry 

Board Irregularity 

Color Variation 

Diameter>6 mm

Evolution

Inflammatory bowel disease (IBD)

Refers to inflammation of the bowel (Small and /or large intestine)

Includes conditions like:

Ulcerative colitis 

Crohn's disease

Colitis

Specifically means inflammation of the colon(large intestine)

Ulcerative colitis (UC): Full Definition

A type of IBD 

One of the most commons forms of IBD 

Affects approximately 1.5 million people in the united states 

A chronic (lifelong) disease 

Affects only the large intestine:

Colon 

Rectum 

Most commonly begin in young adults (20-30s)

Can occur in children and older adults 

Causes ulcers in the mucosa and submucosa 

Inflammation in limited to superficial layers(not full thickness)

Ulcers=eroded tissue→open sores

Ulcerative colitis (UC): causes

Causes ulcers in the mucosa and submucosa 

Inflammation in limited to superficial layers(not full thickness)

Ulcers=eroded tissue→open sores

regions affected Ulcerative colitis (UC) in the large intestine

Affects only the large intestine:

Colon 

Rectum 

Most commonly begin in young adults (20-30s)

Can occur in children and older adults 

Disease pattern: full definition: Ulcerative colitis (UC)

Continunous Inflammation

Starts at the rectum→Spreads upwards 

No “skip lesions”(no normal areas inbetween)

Circumferential involvement 

Affects the entire inner lining around the lumen 

Chronic course with alternating:

Flare (active inflammation and symptoms)

Remission (symptom-free periods)

Continunous Inflammation: Ulcerative colitis (UC)

Starts at the rectum→Spreads upwards 

No “skip lesions”(no normal areas inbetween)

Circumferential involvement: Ulcerative colitis (UC)

Affects the entire inner lining around the lumen 

Chronic course with alternating:

Flare (active inflammation and symptoms)

Remission (symptom-free periods)

Cause/ pathophysiology of IBD

Believed to be autoimmune 

Key features: 

Cytotoxin T cells attack colon lining 

Leads to inflammation and ulceration 

Possible contributing factors 

P-ANCA antibodies (autoimmune maker; may be present)

Gut microbiome changes 

Increase sulfide-producing bacteria 

Associated with inflammation 

Likely due to:

Combination of genetic Predisposition + Environmental triggers 

Cause/ pathophysiology of IBD: Key features

Cytotoxin T cells attack colon lining 

Leads to inflammation and ulceration 

Possible contributing factors 

P-ANCA antibodies (autoimmune maker; may be present)

Gut microbiome changes 

Increase sulfide-producing bacteria 

Associated with inflammation

Likely due to: IBD

Combination of genetic Predisposition + Environmental triggers

Risk factors: IBD

Family history of UC

More common in:

Young adults (teens-30s)

Caucasians 

Eastern European Jewish populations 

Symptoms of IBD

Left lower Quadrant abdominal pain 

Diarrhea 

Often frequent and severe 

May contain blood 

Urgency and tenesmus (feeling of needing to pass stool)

Mechanisms of diarrhea:

Damage to colon→decreased water absorption 

More water remains in stool

Inflammatory bowel disease (IBD)

Refers to inflammation of the bowel (small and /or large intestine)

Includes conditions like:

Ulcerative colitis 

Chron disease

Chron disease 

A type of IBD 

Immune-mediated inflammatory disease (not strictly autoimmune)

Can affect any part of the GI tract:

Mouth→anus

Most commonly affects:

Ileum and colon 

Chronic (lifelong) conditions

Disease pattern of Crohn's disease 

Patchy inflammation (“skip lesions”)

Normal tissue alternating with inflamed tissue 

Cobblestone appearance of intestinal lining 

Transmural inflammation (full thickness)

Mucosa→submucosa→muscle→serosa 

Chronic course with:

Flares (active disease 

Remission (symptom-free periods)

Cause/Pathophysiology of Crohn's disease: full definition

Triggered by an abnormal immune response to gut microbes 

Possible pathogens implicated (theory-based):

Mycobacterium paratuberculosis 

Pseudomonas 

Listeria 

Cause/Pathophysiology of Crohn's disease: Main definition

Triggered by an abnormal immune response to gut microbes

Immune mechanism of Crohn's disease

Antigen Presentation activates T helper (TH1) cells 

Cytokines released:

Interferon-y

TNF-a

Recruitment of Macrophages 

Release of inflammatory mediators:

Proteases 

Free radicals 

Platelet-Activating factor 

Results →uncontrolled inflammation and tissue damage 

Key Pathologic features of chrons disease: Full definition

Granulomas (noncaseating)

May be present,but not always found 

Ulceration 

Deep,crater-like lesions 

Possible defective epithelial barrier 

Allows microbes to cross intestinal lining

Granulomas (noncaseating)

May be present,but not always found

Ulceration

Deep,crater-like lesions 

Possible defective epithelial barrier

Allows microbes to cross intestinal lining

Genetics: of chrons disease 

Strong genetic contribution 

Increased risk with family history 

Key mutations:

NOD2 (CARD15) frameshift mutation 

Leads to abnormal immune regulation

Complications: of chrons disease

Fistulas (abnormal connections between organs)

Strictures (narrowing of bowel lumen)

Bowel obstructions 

Abscess formation

Symptoms: of chrons disease: full definition

Right lower quadrant abdominal pain (ileum involvement)

Diarrhea 

May contain blood 

Malabsorptions (if small intestine involved)

Nutrients deficiencies 

Systemic symptoms:

Weight loss 

Fatigue 

Possible fever

Symptoms: of chrons disease: Systemic symptoms

Weight loss 

Fatigue 

Possible fever

Mechanism of symptoms: full definition

Colon involvement→ Decreased water absorption→ diarrhea Small intestine involvement→ impaired nutrient absorption→malnutrition 

Chronic Inflammation→ pain and systemic symptoms

Mechanism of symptoms: step 1-3

Colon involvement→ Decreased water absorption→ diarrhea 

Small intestine involvement→

Mechanism of symptoms: step 4-6

 impaired nutrient absorption→ malnutrition Chronic Inflammation→ pain and systemic symptoms

Colorectal polyps

Growths of epithelial Cells in the colon or rectum 

Can be non-neoplastic (benign)or neoplactic (precancerous)

Non-neoplastic polyps (benign): types

Hyperplastic Polyps
Inflammatory pseudopolyps 
Hamartomatous polyps 
Mucosal and submucosal polyps 

Non-neoplastic polyps (benign): full definition

Hyperplastic Polyps 

Most common type 

Small,usually in rectosigmoid colon 

Inflammatory pseudopolyps 

Seen in inflammatory bowel disease  

Form during healing after inflammation 

Not cancerous 

Hamartomatous polyps 

Disorgnized but normal tissue 

Associated with genetic syndromes (Peutz-Jeghers,Juvenile polyposis)

Mild or syndrome-dependent cancer risk 

Mucosal and submucosal polyps 

Usually Small and incidental 

Clinically insignificant 

Hyperplastic Polyps

Most common type 

Small,usually in rectosigmoid colon

Inflammatory pseudopolyps

Seen in inflammatory bowel disease  

Form during healing after inflammation 

Not cancerous

Hamartomatous polyps

Disorgnized but normal tissue 

Associated with genetic syndromes (Peutz-Jeghers,Juvenile polyposis)

Mild or syndrome-dependent cancer risk 

Mucosal and submucosal polyps

Usually Small and incidental 

Clinically insignificant

Neuplastic Polyps (precancerous): types

Adenomatous polyps (asked on exam)
Serrated polyps (asked on exam)
Adenoma-Carcinoma sequence (Push arrow)
Colorectal cancer
Types (asked on the Exam)
Tubular: lower malignant risk 

Tubulovillous: intermediate risk 

Villous: highest malignant risk

Types (asked on the Exam): Neuplastic Polyps (precancerous) RISK SPECIFIC

Tubular: lower malignant risk 

Tubulovillous: intermediate risk 

Villous: highest malignant risk

Adenomatous polyps (asked on exam)

Most common/most important (90-95% effected)

Most important precancerous Polyps 

Often Associated with APC turmor suppressor gene mutation 

Cancer Risk increases with larger size and villous histology

Serrated polyps (asked on exam)

Flat or sessile with saw-tooth appearance

causes:DNA methylation leads to gene silencing 

Can progress to colorectal cancer via the serrated pathway 

Adenoma-Carcinoma sequence (Push arrow)

APC Mutation→ loss of growth control→ early Adenoma (polyp formation)

KRAS mutation→ increased cell proliferation→late adenoma growth 

P53 Mutation→ loss of tummer suppression and apoptosis→carcinoma (cancer formation) Happens through gene mutation

Colorectal cancer

Most commonly Adenocarcinoma 

Usually occurs in patients over age 50 

Third most common cancer worldwide

Risk factors of Colorectal cancer

genetic/disease-releated 

Familial adenomatous Polyposis(FAP)

Inflammatory bowel disease (especially ulcerative colitis)

Lynch syndrome (inherited condtion→ increased colorectal cancer risk at younger age)

Lifestyle/risk factors: of Colorectal cancer

Obesity 

Smoking

Alcohol use 

High red/processed meat diet 

Low fiber intake 

Other 

Acrimegaly 

Increased COX-2 activity

Left sided: Colon Cancer

Causes obstruction 

Narrow Stools 

Constipation

Abdominal pain 

Hematochezia