Cell pathology

Medicine Smd 535 with Koles at Wright State University

About this deck

By: Anonymous
Textbook:

Robbins & Cotran Pathologic Basis of Disease: With STUDENT CONSULT Online Access (Robbins Pathology)
Created: 2011-08-20
Size: 39 flashcards
Views: 6

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Five causes of pathologic atrophy

Disuse
Denervation
Decreased blood supply or hypoxia
Malnutrition
Pressure

Cellular mechanism of atrophy (2)

Upregulation of ubiquitin proteosome pathway

Increased autophagy in lysosomes

Lung Metaplasia

Columnar to Squamous

Bronchial epithelium of smokers

Esophageal Metaplasia

Squamous to Columnar

Caused by chronic acid reflux

7 Causes of Cell Injury

Hypoxia
Ischemia - Worse (why?)
Physical/Chemical
Infection
Genetic defects
Nutritional Imbalance
Immune Reactions

3 Sequential changes in cell death

Nuclear Condensation

Membrane blebbing leading to fragmentation - caused by cytoskeletal destruction

Swollen mitochondria and other organelles - mito deposits means death for sure

Reversible Cell Injury

Loss of Microvilli

membrane Blebs

mildly dilated mito

Nuclear clumping

ribosome detachment

Irreversible Cell Death

Rupture/fragmented PM

Severely swollen Mito w dark deposits

Pyknotic nucleus

Necrosis Definition

Cell death resulting from severe damage cell's proteins, organelles, or membranes. Results in enzymatic destruction of contents and leakage into environment. ALWAYS causes inflammation.

Coag necrosis

Denaturation of structural and enzymatic proteins, leading to cell lysis

Observed in ischemic injuries - except CNS

Karyolysis - nuclear fading, Frayed PM, ghosted dead cell outlines

Liquefaction

Complete digestion of cells, creates a gelatinous mass, could be supporative.

Seen with bacterial infection (toxins digest cells) or intense leukocyte response (cell enzymes digest). Indicative of CNS ischemia.

Caseous

A form of coag - granulomatous inflammation. Cheesy and yellowish - friable.

Central necrosis surrounded by macros and lymphocytes (TH1 cells).

Mycobacterial and fungal infection.

Gangrenous

Coag necrosis involving a large part of the body (usually a limb).

Dry - no infection. Wet - infected.

NOT gas gangrene from C perfringens

Fat necrosis

White a chalky deposits.

Lipase released from inflamed pancreas digests lipids. Fatty acids complex w Ca, creating the deposits.

3 Causes of liquefaction necrosis

Bacterial Infection with toxin release

Intense inflammatory response - leukocyte enzymes

Ischemia in CNS

2 Major causes of Caseating necrosis

Mycobacterium - mostly TB (NOT mycobacterium marinum or leprae)

Fungi is the other one

NOT Caseating - sarcoidosis, brucellosis, tatoos

The 5 mechanisms of cellular injury

ATP depletion
Mito damage
Loss of Ca homeostasis
ROS
Membrane Damage

ATP Depletion - How it kills

Ischemia/Hypoxia reduce O2 available for ATP via Ox Phosph

Less ATP - NaKATPase pump stops - Cell potential fails - cell swells - membrane damage

Ca pump (2nd active trans) also fails. Extra Ca opens Mito pore

Ribosomes detach - misfolded protein resp

Mito Damage - how it kills

Mito pore in inner membrane opens under various stimuli. Open pore wrecks gradient - ends ATP production. Increased mito permeability releases cytochrome C - a pro apoptotic signal activating caspases. Mito damage - increases ROS (cant reduce O2)

Loss of Ca homeostasis - how it kills

Cyto Ca increases after injury - released from organelles and through PM.

High [Ca] will directly activate:

Phospholipases - PM damage
Proteases - Disrupts cytoskeleton
Endonucleases - nuclear damage
ATPase - no atp...

ROS Generation

Ox phosph, radiant energy, inflammation, damaged mito

Fentonn rxn - Fe donates electrons to O2 - makes a radical

Superoxide made into H2O2 by SOD.

H202 reacts w Fe to make ROS

ROS Removal - Antioxidants

Glutathione reductase - mito
SOD - Mito
Catalase - peroxisomes

ROS Removal - Scavenging

Vitamins - A C E (ace free radicals)

Ferritin - Fe storage

Transferrin - Fe transport

Ceruplasmin - Cu storage and trnas

Membrane Damage - How it kills

Cytoskeletal damage - destabilizes membrane

Mechanisms - ROS, decreased phospholipid production, increased phospholipid degradation

Worst are mito, lysosome and PM

The 2 big defects in all irreversible cells

1) Inability to fix or reverse mito dysfunction

2) Severely disrupted membranes

Why is ischemia worse than hypoxia alone

No blood means no O2 AND no glucose for energy. No Glucose for glycolysis - run out of ATP WAY faster. No ATP means cell death. (How?)

2 Opposing effects of reperfusion injury

1) Promotes survival of SOME reversibly injured cells

2) Flushes the drain circlers

3 Mechanisms causing reperfusion injury

1) Reperfusion brings in O2 - makes ROS

2) Injured Mito - can't reduce O2 completely - makes ROS

3) Inflammation is amplified - hypoxic cells make cytokines to activate endothelium Damaged endothelium increases adhesins - both bring in more leukocytes

Direct toxins

No modification needed.

Usually damages GI and Kidney

Indirect toxins

Chemical not biologically active - usually converted in SER of hepatocytes by cytochrome P450.

Cause liver damage

Acetominophen OD

Depletes hepatocyte glutathione, resulting liver necrosis from mito damage

Extrinsinc Apoptosis Pathway

Stimuli - death receptor bound (Fas/FasL, TNF) - activates initiator caspases - activate executioner caspases: endonuclease, cytoskeleton breakdown, protein degradation. Breaks into apoptotic bodies for phagocytosis

Intrinsic Apoptotic Stimuli

GF withdrawl, DNA damage, Protein misfolding (ER stress)

Intrinsic Apoptosis Pathway

Stimuli removes BCL (antagonists) - allows Bax and bak (agonists) to bind. Bax & Bak open mito pore (increase permeability) - allow pro-apoptotics out (cytochrome C). Caspases activated due to pro-apoptotic shifted balance.

3 Promoters of Phagocytosis (for apoptosed cells)

PS on outer leaflet

Thrombospondin coating

Ab and complement

Dystrophic Calcification

Local Deposition of Ca in non viable tissue despite normal blood Ca levels

Metastatic Calcification

deposition of Ca in normal tissue w high blood calcium

PTH imbalance - neoplasia

Homociderin

Hemachomatosis

Homogenticic Acid

Alkaptonuria, Ochronosis

About this deck

By: Anonymous
Textbook:

Robbins & Cotran Pathologic Basis of Disease: With STUDENT CONSULT Online Access (Robbins Pathology)
Created: 2011-08-20
Size: 39 flashcards
Views: 6

About StudyBlue

“Simply amazing. The flash cards are smooth, there are many different types of studying tools, and there is a great search engine. I praise you on the awesomeness.”
Dennis