Gen path week 8 (necrosis and cellular accumulations)

Sammy

Three methods of cell death

Necrosis

Apoptosis

Pyroptosis

Necrosis

Accidental cell death

Problematic (inflammatory can become chronic)

Apoptosis

Preferred method of cell death

no inflammation

Pyroptosis and where do you see it

Programmed cell death but WITH INFLAMMATION

-seen primarily in inflammatory cells (macrophages)

When does necrosis patterns occur and what is the exception

Ischemia, iatrogenesis and infection

-none of necrotic patterns apply if cell death occurred by apoptosis

What is hydropic change

AKA cloudy swelling

-when water goes into cell and changes it's shape

Is hydropic change reversible?

Yeth

When is it no reversible?

When nucleus is damaged

Pyknosis definition

Visible change in appearance of nucleus —> nuclear destruction leading to apoptosis (cell is done)

What is apoptosis dictated by

Dictated by the mitochondria (interstitial, intracellular and intravascular)

Coagulative necrosis (ISCHEMIC)

Cell death with preservation of basic cell outline

Where is coagulative necrosis seen

Myocardial infarction —> death by ISCHEMIA

Liquefactive necrosis (CELL LYSIS)

Cell membrane dissolves due to BACTERIAL lysis or autolysis

What is liquefactive necrosis done by

Neutrophils —> leads to pus formation

Where do you see liquefactive necrosis

Brain cell death

Caseous necrosis (CHEESY)

Combo of coagulative (ischemia) and liquefactive (cell lysis)

Where is caseous necrosis seen

TB (granuloma)

What is gangrenous

Combo of ischemia (coagulative) and microbial putrefaction of flesh (liquefactive)

What is dry gangrene

Ischemia predominates: no infection with loss of blood flow

What is wet gangrene

Ischemia plus bacterial lysis: infection with loss of blood flow

What is gangrene associated with

Frostbite and diabetes

Enzymatic fat necrosis occurs where and does what

Occurs with pancreatic injury where digestive lipases spill into CT supportive elements (starts digesting itself)

Fibrinoid necrosis

Cell death occurs in environment with serum complement activation and fibrin deposited in the vessel wall

What is symptom of firbrinoid necrosis

Bleeding

What is fibrinoid necrosis associated with

Vasculitis from type 3 hypersensitivity (lupus)

What is cellular accumulation

Edema that occurs with or without inflammation

Exudate

Fluid leaving blood vessels with inflammation

Transudate

Non-inflammatory edema due to imbalance of starling's forces in capillary (swelling without injury)

Where do you see accumulation of unwanted material in tissues WITHOUT inflammation

Intracellular and interstitial build-up

Is intraceullar accumulation more severe/symptomatic or interstitial

Intracellular because unit of life failing to maintain internal constancy

Where do cellular accumulations come from?

-Created by disease or cellular dysfunction

-Accumulations themselves can cause disease of dysfunction

Where does hydrostatic pressure come from?

Created by presence of water

Where does osmotic/oncotic/colloid pressure come from?

Created by presence of plasma albumin (protein from liver)

Is hydrostatic or oncotic pressure stronger

Hydrostatic (why we have lymph to balance out extra fluid coming out of cell from hydrostatic pressure)

How can transudate form (3)

1. Increased hydrostatic pressure

2. Decreased osmotic pressure

3. Lymphatic obstruction

Examples of increased hydrostatic pressure (2)

-Congestive heart failure backflow

-Increased total body water seen with kidney disease

Examples of decreased osmotic/oncotic pressure (3)

-hypoalbuminemia seen in cirrhosis (chronic hepatitis) —> ascites (edema in abdominal cavity)

-kwashiorkor (protein deficiency in kidney —> ascites)

-marasmus (caloric malnutrition)

Lymphatic obstruction examples

Elephantiasis

Metastatic cancer cells

Elephantiasis is caused by

Mosquito bites/ parasitic worm

What do metastatic cancer cells do

Block lymph flow from moving cancer cells

Exudate

Edema WITH inflammation due to increased capillary permeability

-anasarca (extreme generalized swelling)

-myzedema (severe hypothyroidism characterized by swelling and thickening of skin)

What are other cellular accumulations (3)

Lipids

Minerals

Amyloid

Accumulation of lipid examples (3)

Steatosis, sphingolipidoses and lipofuscin

Steatosis

Intracellular fat accumulation (always pathological when outside adipocyte)

-also known as fatty liver

Why is liver a common location for steatosis

1. Naturally metabolizes and processes fats

2. It is frequently altered in function due to alcohol and viruses

Sphingolipidoses

Genetic disorders creating accumulations through enzyme deficiency and substrate accumulations

Example of sphingolipidoses

Tay-sachs disease: neurodegenerative disorder where there excess accumulation of gangliosidosis (sugar+lipid) in brain and nerves and retina (HALL MARK CHERRY RED SPOT IN RETINA)

Lipofuscin

Brownish pigment due to breakdown or damage of intracellular or extracellular material

-build up of oxidized proteins, lipids and metals that accumulate in lysosomes of cells as people age

What are liver spots

Color looks like liver tissue, caused by lipofuscin

What can lipofuscin also cause

Interfere with cell function and generate ROS

What are the mineral accumulations for this class (4)

Calcium, heavy metals, iron and copper

Difference between dystrophic and metastatic calcification

Dystrophic is calcium in damaged tissues (normal levels of calcium) while metastatic is normal levels of ca and infiltration into normal tissues

Examples of dystrophic calcification (idk if we need to know this)

Calcification of aorta and atherosclerosis

Examples of metastatic calcification (idk if we need to know this)

Hypervitaminosis D and hyperparathyroidism

What're the 3 heavy metals

Lead, methyl mercury and ethyl mercury

Is methyl mercury neurotoxic or is ethyl mercury neurotoxic

Methyl is bad

Which one is iron overload: hemosiderosis or primary hemochromatosis

Primary hemochromatosis

What is hemosiderosis and examples

Mild iron overload contained in local area due to dead RBC's

-EX: bruise or seen in spleen with RBC breakdown

What is primary hemochromatosis

Severe iron overload from genetic mutation which allows too much iron to build up and be stored in cells

What will people with primary hemochromatosis look like

Bronzing of the skin which can appear metallic or greyish

What is wilson's disease

Genetic disorder that affects body's ability to transfer copper out of the body —> damage liver and nerves

What is hallmark sign of wilson's disease

Kayser-fleischer rings appear in the eyes

What is amyloidosis

Amyloid proteins are misfolded proteins and aggregate into insoluble amyloid fibrils (toxic bc can't be eliminated)

What happens when amyloid deposits happen in the brain

Leads to dementia due to inflammation (alzeimer's)

What happens with misfolded proteins

-amino acids make beta pleated sheets rather than alpha

-beta sheets stack together and form fibrils —> can't be eliminated

What is multiple myeloma and what cells become cancerous

Most common cancer to originate in the spine/flatbones (cancer of plasma cells)

Where does multiple myeloma originate

Bone marrow

Describe what happens in multiple myeloma

Stem cells make faulty B cell due to genetic mutation which allows—> plasma cell proliferates abnormally and makes excessive amounts of IG light chains and build up and crowds out healthy cells

Where do the multiple light chains fragments accumulate

Urine

Bence jones proteinuria AKA and definition

When light chains accumulate in kidneys

-AKA = monoclonal immunoglobulin or M-protein

What is multiple myeloma in blood called and what does it look like

Rouleaux formation

-RBCs stack like coins