Block 2 Flashcards

Question

HYPERTROPHY Why wouldn't we see this in cells that repliate often?

Answer 1

- They can just increase in numbers (hyperplasia) if they are dividing all the time!

Answer 2

exercise, pregnancy *bigger cells!

Answer 3

Pathologic Hypertrophy: cardiac hypertrophy associated with CHF - Disturbance in aortic outflow (any other pathology) - Left ventricle compensates through hypertrophy to increase muscle to help get blood out

Answer 4

**Concentric: **Thickening of wall and smaller chamber - Hypertrophic growth of ventricle - Decrease amount of volume of ventricle chamber - Dysfunction of diastolic filling **Hypertrophic cardiomyopathy (HCM)** seen frequently in cats

Answer 5

**Eccentric: **Thinning of wall and larger chamber - Dilation of ventricle without thickening of the ventricles - Decreased systolic function **Dilated Cardiomyopathy (DCM) in Dogs**

Answer 6

Cardiac hypertrophy (different causes/mechanisms) * limit beyond which enlargement of muscle mass is no longer able to cope with the increased burden →several regressive changes occur in the myocardial fibers ( e.g. lysis and loss of myofibrillar contractile elements) * extreme cases →myocyte death

Answer 7

-increased workload, e.g. the bodybuilder's skeletal muscle. -ormone stimulation, e.g. the pregnant uterus (smooth muscle hypertrophy)

Answer 8

-increased resistance e.g.cardiac muscle hypertrophy as a result of working against an increaded peripheral resistance in hypertention (high blood pressure) -physical obstruction, e.g. bladder smooth muscle hypertrophy in outflow obstruction caused by an enlarged prostate gland.

Answer 9

An increase in number of cells in an organ or tissue Seen in cells that divide frequently

Answer 10

Physiologic: mammary glands, bone marrow (only normal in young animals) Ex. mammary glands get bigger during pregnancy for breastfeeding, after hepatectomy (liver removal), hepatocytes can replicate to form new liver tissue

Answer 11

Pathologic: excessive hormones or growth factors Ex. gingival hyperplasia, epidermal thickening (repeated irritation) *thyroid gland

Answer 12

Those that routinely proliferate in normal circumstances, such as those of the **epidermis, intestinal epitheliem and bone marrow** cells. readily become Hyperplastic +++

Answer 13

such as n**eurons and cardiac and skeletal muscle**, myocytes, have very little capacity to regenerate or become hyperplastic in most situations +

Answer 14

such as **bone, cartilage and smooth musle**, are intermediate in their ability to become hyperplastic ++

Answer 15

Myostatin : protein produced my myocytes that inhibits myocyte growth differentiation and growth Whippets can have a mutation of the myostatin gene which involves a two-base-pair deletion, and results in a truncated, inactive, myostatin protein

Answer 16

**Change in phenotype** of an already differentiated cell (*what a cell looks like) - due to chronic irritation (stress) - may decrease function - increases chance of transforming into malignant/neoplastic cells - look for this on **histology!!**!

Answer 17

**Reversible if the cause of irritation is removed** - Ex. Irritation to the lungs from smoking - Ex. **Vitamin A **deficiency in chickens

Answer 18

Tissue : Chicken Oesophagus Process: metaplasia Morphological Description: severe multifocal mucous gland squamous metaplasia Aetiology : Vit A deficiency

Answer 19

Abnormal development (cell had not differentiated yet) Change in cell **shape, size and organization **- becomes disorganized Commonly affecting epithelial cells and *associated with neoplastic process*

Answer 20

**Hypoplasia: **incomplete development or underdevelopment of a tissue/organ - Cells never fully developed/always have been small Ex. **Cerebellar Hypoplasia Ǖ Feline Panleukopenia Virus**

Answer 21

Aplasia: lack of the development of an organ or tissue literally just didn't show up to the party

Answer 22

Hypotrophy: progressive loss of function of tissue

Answer 23

Disruption of homeostasis stress or stimulus was too intense to adapt Reversible or Irreversible Many Causes: Bacteria, fungi, viruses (infectious) Hypoxia or anoxia Immune-mediated diseases Genetics Aging Toxicity **Most common: oxygen deficiency infectious agents common/important immunological dysfunction**

Answer 24

* Hypoxia: **partial reduction** in O2 (oxygen) delivery to a tissue

Answer 25

**no** O2 (oxygen)delivery to a tissue

Answer 26

1 inadequate oxygenation of blood 2 reduced transport of O2 in blood 3 reduction in blood supply=ischema 4 blockage of the cell respiratory enzymes

Answer 27

heart failure respiratory failure

Answer 28

Anemia carbon monoxide toxicosis

Answer 29

Thrombosis

Answer 30

**cyanide toxicosis**

Answer 31

anoxic damage to muscles of the hind limbs

Answer 32

Viruses bacteria fungal (mycosis) protozoan metazoan parasites

Answer 33

‒ Obligate intracellular “parasites”use host cell enzyme systems ‒ Cell survival depends on method viruses leave the cell

Answer 34

‒ Toxins ‒ Overwhelming and uncontrolled replication

Answer 35

Progressive, chronic inflammatory disease

Answer 36

‒ Replicate in specific host cells -->cell destruction

Answer 37

‒ Inflammation, tissue distortion, utilization of host nutrients

Answer 38

Immune system fails to respond or Immune system over-responds or aberrant reaction

Answer 39

- Congenital defects: Severe Combined Immunodeficiency (SCIDS, Arabian foals) antigen receptors(lymphocytes) - Acquired defects - May be transient (but not always) : Results from damage to lymphoid tissue : Viral infections, Chemicals, Drugs

Answer 40

Immune system over-responds or aberrant reaction - Autoimmune diseases - Hypersensitivity reactions : anaphylaxis, Flea allergy dermatitis, Feline asthma

Answer 41

Depletion of ATP Mitochondrial change Loss of calcium homeostasis Oxidative stress Membrane permeability DNA and protein damage *** Lots of these mechanisms overlap do not get too caught up in the nitty gritty details!

Answer 42

Cells need ATP as their form of energy to carry out their functions **What happens if ATP is lost?** - 5-10% loss ĺ **VERY BAD** **Failure of the Na+/K+ Pump** Cell membrane damage ĺ loss of gradients (influx of Ca2+, H2O and Na+, Efflux of K+) Swelling of ER **Altered Cell metabolism** Consistently in a state of anaerobic glycolysis Build-up of lactic acid Depletion of glycogen stores **Detachment of Ribosomes** Decreased protein synthesis

Answer 43

Damage to the mitochondria will lead to the formation of the **mitochondrial permeability transition pore** (MPTP) **What happens when the pore opens?** Membrane potential is lost - ATP depletion from failure of oxidative phosphorylation **Increased Reactive Oxygen Species (ROS)** Released from the mitochondria into the cytoplasm **Activation of Apoptosis** Apoptotic activating proteins leak out and cause programmed cell death

Answer 44

Calcium is an ion found in higher concentrations extracellularly If too much calcium builds up intracellularly, different signaling cascades may occur

Answer 45

How can calcium accumulate? Release from the ER or the mitochondria Damage from outside of the cell

Answer 46

What happens when calcium accumulates inside the cytoplasm? Activation of enzymes ĺ **phospholipases, proteases, endonucleases and ATPases* (EUHDNVGRZQ$73«OLN**(breaks down ATP...like girl c'mon seriously?) Opening of the **MPTP** leading to even more decreased ATP!

Answer 47

Can be physiologic or pathologic

Answer 48

Physiologic Ǖ A byproduct produced by the mitochondria during cellular respiration Pathological Ǖ released by activated WBCs during inflammatory responses

Answer 49

ROS are normally removed by scavenging mechanisms - Ex. Antioxidants like Vitamins A and E help remove ROS

Answer 50

****ROS are normally removed by scavenging mechanisms - Ex. Antioxidants like Vitamins A and E help remove ROS

Answer 51

Increased production causes oxidative stress and decreased scavenging

Answer 52

- radiation, toxins, inflammation, aging, degenerative diseases, etc.

Answer 53

**Membrane damage, oxidative modification of proteins, DNA damage**

Answer 54

* Inflammation (lecs to come) * Transition metals (ie. Iron, Copper) * Nitric oxide (NO) * Absorption of radiant energy

Answer 55

* Inflammation (lecs to come) * Rapid bursts of ROS produced by activated WBCs (esp. neutrophils) - generatessuperoxide anion (O2 *- )

Answer 56

* Transition metals **(ie. Iron, Copper)** * Frequently donate or accept free electrons * **Catalyze free radical formation**

Answer 57

* Nitric oxide (NO) * Important chemical mediator * Generated by endothelial cells, macrophages, neurons, and others * Can act as a free radical * Can be converted into peroxynitrite anion ONOO- , or NO2, or NO3

Answer 58

* H2O + **ionizing radiation ***OH + H

Answer 59

Spontaneous decay: O2 * + H2O O2 + H2O2 Enzymes Storage and transport proteins Antioxidants - Vitamin E, Vitamin A, glutathione

Answer 60

O2 + H2O O2 + H2O2

Answer 61

Enzymes: catalase,superoxide dismutase, glutathione peroxidase ‒ Break down H2O2 and O2 ‒ Located near sites where oxidants are formed

Answer 62

Storage and transport proteins - transferrin, ferritin, ceruloplasmin ‒ **Bind reactive metals: Fe, Cu**

Answer 63

Antioxidants - Vitamin E, Vitamin A, glutathione ‒ Block initiation ‒ Inactivate (scavenge)

Answer 64

lipid peroxidation in membranes oxidative modification of proteins lesions to DNA

Answer 65

extensive membrane damage

Answer 66

damage active sites, change conformation, enhance degradation -**generated by monamine oxidase (MOA) in outer nmitochondrial membrane**

Answer 67

cell aging, malignant transformation -MOA: single or double stranded breaks, cross-linking of DNA strands, formation of adducts

Answer 68

All membranes ĺ plasma membrane, mitochondrial membrane and lysosomal

Answer 69

ROS Decreased synthesis of phospholipids Decreased production of ATP Increased breakdown of phospholipids ĺ Phospholipases! cytoskeletal abnormalities

Answer 70

decreased phospholipid synthesis: secondary to defetive mitochondrial function and/or hpoxia decreased production of ATP--> decreaded phospholirid synthesis

Answer 71

increased phospholipid breakdown: activation of calcium dependent phospholipases accumulation of lipid breadksown products

Answer 72

-increased cytosolic calcium -->activation of proteases-->damage to cytoskeleton

Answer 73

Plasma Membrane: loss of cellular contents ion and fluid (osmotic) imbalance

Answer 74

Mitochondrial Membrane: MPTP opening leads to the leakage of pro-apoptotic proteins

Answer 75

Lysosomal Membrane enzyme leakage leading to digestion of proteins and nucleic acids

Answer 76

**Accumulation of misfolded proteins ‒ Genetic mutations ‒ Free radical damage Cells have repair mechanisms for misfolded proteins When overwhelmed proteins accumulated in the ER →“ER stress” initiates apoptosis**

Answer 77

**Radiation, cytotoxic anticancer drugs, hypoxia ‒ Direct damage ‒ Free radical damage Cells have repair mechanisms When overwhelmed initiates apoptosis**

Answer 78

Reversible Cell swelling (Hydropic Degeneration) Lipidosis (fatty change) Catch it early or its **GAME OVER**

Answer 79

Irreversible Necrosis Apoptosis

Answer 80

cells have a limited repertoure of responses to injury, depending on the celltype and the nature of teh injury 1-adaption (increase efficiency or productivity) 2-degeneration (diminished functinal capacity) 3-death

Answer 81

Ballooning Degeneration Swinepox Virus reversible

Answer 82

Can be called "hydropic degeneration" or ballooning degeneration (specifically in epidermis) Increase in the size and volume of the cell **"bulging"

Answer 83

How does this happen? Loss of ionic and fluid homeostasis Influx of fluid into the cell leading to cell swelling

Answer 84

Causes: Hypoxia - how does this cause it? (lack of oxygen which means lack of ATP) Toxins

Answer 85

Which cells are commonly affected? - Cardiomyocytes - Hepatocytes - Proximal Tubule epithelium - Neurons

Answer 86

- **Pale** in color (pallor) - Wet - Swollen with smooth edges find

Answer 87

1.Plasma membrane alterations 2.Mitochondrial changes 3.Dilation of the ER 4. Nuclear alterations

Answer 88

1.Plasma membrane alterations,such as blebbing, blunting, and loss of microvilli

Answer 89

2.Mitochondrial changes, including swelling and the appearance of small amorphous densities

Answer 90

3.Dilation of the ER, with detachment of polysomes; intracytoplasmic myelin figures may be present (see later)

Answer 91

4. Nuclear alterations, with disaggregation of granular and fibrillar elements

Answer 92

release of Ca from the endoplasmic reticulum

Answer 93

-presence of inrracytoplasmic fally vacculation -can be seen with cell swelling

Answer 94

Etiology: hypoxia, toxicity or metabolic disorders **Abnormalities in the synthesis, utilization and/or mobilization of fat**

Answer 95

Pathogenesis: impaired metabolism of Fatty Acids leads to the accumulation of lipids - formation of fat vacuoles

Answer 96

Which cell are more susceptible? Cardiac and skeletal muscle, liver (hepatic lipidosis), kidneys Liver is most central organ to lipid metabolism - all these cells need a ton of energy: use fats for energy

Answer 97

How does lipidosis occur? ** Excessive delivery of FFAs** from fat stores or diet **Decreased oxidation of FFAs** (not being oxidized into ketone bodies to be used!) **Impaired synthesis of Apoprotein** **Impaired combination of protein and triglycerides** to form lipoproteins (need to be in this form to be transported) ** Impaired release of lipoproteins** from hepatocytes main causes: hypoxia, toxicity, metabolic disorders

Answer 98

- Can be yellow/pale - Rounded edges - Greasy texture - Soft

Answer 99

Looks like fat! Large cytoplasmic vacuoles **DISPLACES THE NUCLEUS TO THE PERIPHERY**

Answer 100

Seen frequently in mini horses Also seen in ruminants and cats

Answer 101

**Physiologic in Ruminants:** Undergo small amounts of hepatic lipidosis to form ketone bodies to keep up with their energy requirements ** Pregnancy toxemia and early lactation** -very high energy requirements

Answer 102

Pathological: obesity (fat accumulation), starvation causing mobilization of fat (liver gets overwhelmed processing all the fat and it can accumulate in the liver) and diabetes also causes mobilizationof triglycerides

Answer 103

Can be fatal: Death of hepatocytes is irreversible - liver dysfunction

Answer 104

Necrosis: cell death from irreversible injury by hypoxia, ischemia and direct cell membrane injury

Answer 105

Plasma membrane damage *does not stay intact* Swelling of the mitochondria and lysosomes *as well as cell* **USUALLY ACCOMPANIED BY INFLAMMATION UNLIKE APOPTOSIS ***cell shrink/membrane intact* * **If you can see inflammation (redness/swelling) you can assume its necrosis!!**

Answer 106

Biochemical alterations occur first! Ultrastructural changes - occur in <6 hours Histological Changes - 6-12 hours Gross changes - 1-2 days Loss of Cell Nuclei Karyolysis: nuclear fading 3 Pyknosis: nucleus shrinks 1 Karyorhexis: nuclear 2 fragmentation *you have gotten skinn/shrink. I can pick you up* Know the attached chart!

Answer 107

Pale Soft Visible zone of inflammation MDx: hepatitis, multifocal coalescing, Inflammation yes Etiology: histomonas meleagridis Disease Name:"blackhead"

Answer 108

**Losing basophilia**, binding of eosin to denatured proteins **turns pick** **Enzyme digested organelles **- Vacuolation and moth-eaten appearance **Calcification **may occur

Answer 109

Mainly seen in liver, heart, kidney, skeletal muscle Why? Response to h**ypoxia or ischemia** Can be a response to toxic injury **Always think of INFARCTS: local areas of coagulative necrosis**

Answer 110

Histology: Necrotic cells are surrounded by phagocytic WBCs - neutrophils and macrophages

Answer 111

Unique to** CNS** due to high presence of lipids in the brain - Dead cells digested and are transformed into a mass of liquid (PUS!!!) Leukoencephalomalacia: Leukomyelomalacia: Polioencephalomalacia: Poliomyelomalacia: **All of these can overlap!**

Answer 112

Leukoencephalomalacia: necrosis of **white **matter of the **brain**

Answer 113

Leukomyelomalacia: necrosis of **white** matter of the **spinal cord**

Answer 114

Polioencephalomalacia: necrosis of **grey** matter of the** brain**

Answer 115

Poliomyelomalacia: necrosis of **grey **matter of the **spinal cord**

Answer 116

Etiology? Thiamine (B1) deficiency Lead poisoning Polioencephalomalacia

Answer 117

Etiology? Ingestion of Moldy corn containing Fusarium verticilioide Leukoencephalomalacia

Answer 118

Etiology? Equine herpesvirus 1 Rabies (lyssavirus) West Nile Virus (Flavivirus) Poliomyelomalacia

Answer 119

**Usually begins as coagulative necrosis** - affects distal extremities - **Frostbite****

Answer 120

**Dry gangrene**: no bacterial infection- tissue appears very dry **Wet gangrene**: bacterial infection that makes tissue appear wet - mastitis goat (wet); Clostridium novyi

Answer 121

Caseous = **CHEESE** - White necrotic debris Associated with bacteria that can replicate in phagosomes Ǖ hard for body to get rid of! Ex. **Mycobacterium,** Cornyebacterium pseudotuberculosis Ex. **Tuberculosis** Histology: Eosinophilia of necrotic area with a rim of inflammatory cells -** NO NEUTROPHILS**

Answer 122

Enzymatic Necrosis Traumatic Necrosis of Fat Abdominal Fat Necrosis Saponification

Answer 123

Enzymatic Necrosis **- Pancreas**, commonly following repeated pancreatitis - Lipases become activated and destroy surrounding adipocytes

Answer 124

Traumatic Necrosis of Fat: - Trauma to tissue can lead to necrosis of surrounding fat Ex. Surgery, Dystocia (difficult birth)

Answer 125

- idiopathic or possibly related to vitamin E deficiency - seen in the omentum, mesentery and retroperitoneum - may cause intestinal stenosis *(narrowing)* in extreme cases (lumen of intestines becomes narrow)

Answer 126

Saponification: Fat necrosis where calcium deposits in an injured area

Answer 127

Antigen antibody complexes accumulate and deposit in the walls of arteries following immune reactions (**TYPE III HYPERSENSITIVITY)** - **Fibrinoid = Fibrin + Antigen-Antibody** complexes Looks like fibrin on histology - very strandy!

Answer 128

**Programmed cell death** - Cells will activate enzymes to degrade **their own DNA and proteins** - apoptotic cells break up into fragments, called **apoptotic bodie**s, which contain portions of the cytoplasm and nucleus - **plasma membrane stays intact**

Answer 129

**No inflammation!! - make sure you know this!**

Answer 130

Physiological: **embryogenesis**, thymus involution Pathological: Viral infection, Extensive DNA damage, accumulation of misfolded proteins

Answer 131

**Cell shrinkage** with increased cytoplasmic density ** Pyknosis:** chromatin condensation Formation of **cytoplasmic blebs and apoptotic bodies** Phagocytosis of apoptotic cells by adjacent healthy cells

Answer 132

Intrinsic Pathway Cytochrome C Extrinsic Pathway

Answer 133

Intrinsic Pathway -** major mechanism of apoptosis** - increased mitochondrial permeability and release of pro-apoptotic molecules (death inducers)

Answer 134

- Cytochrome C:released into cytoplasm to initiate suicide - "point of no return"-->activation of **caspases** **Initiators:** Caspases 8 and 9 **Executioners:**Caspases 3 and 6

Answer 135

Extrinsic Pathway - Initiated by death receptors (TNFs) 2 present on every cell! - some substances bind to these receptors, bind and activate caspases

Answer 136

- Shrinkage - **Plasma membrane remains** intact - - Increased density of cytoplasm

Answer 137

- Edible for phagocytes - **Expressed phospholipids** in the outer layer of the membrane in order to be identified by macrophages - May become coated with natural antibodies & proteins of the complement system

Answer 138

- secrete substances that recruit phagocytes - some express **thrombospondin,** which is easily identified by phagocytes) - macrophages may produce proteins that bind to apoptotic cells for engulfment

Answer 139

Too Little Apoptosis **Mutation in p53 gene**(tumor suppresor gene) Defective apoptosis and increased abnormal cell survival Leads to proliferation of neoplastic cells and thus, **neoplasia is a common consequence**

Answer 140

Too Much Apoptosis: Neurodegeneration and ischemia

Answer 141

-pathological process location **distribution(must, duration and severity (optional)**

Answer 142

-pathologic process location **cause**

Answer 143

distribution<--locally, extensive, process<--necrotizing hepitatis-->organ/location Edx: Clostridial Hepatitis