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100 Cards in this Set

  • Front
  • Back
Pathogenesis
Mechanism of Disease
Cell injury leads to...
Degeneration

Necrosis

Apoptosis

Neoplasia
Cell Adaptation leads to...
Metaplasia

dysplasia
Cell injury- causes
Hypoxia, Ischaemia

Disturbed Metabolism

Genetic damage
Damage to cell membrane...
Osmotic Disruption

Damage to ion pumps

Loss of shape- cytoskeleton

DNA damage

Mitochondrial damage---> dec ox phosph, anaerobic glycolysis, ATP depletion

ATP depletion---> Ion pump disruption---> osmotic swelling
Degeneration

eg
Reversible, non lethal change

Cloudy swelling---> hydropic/ vacuolar degen---> eg fatty change
Fatty change

Normal during--->

Pathological --->
Parturition and lactation in ruminants, neonates

Toxaemia, protein malnutrition, starvation (mobilisation)/ excess dietary fat, lipotrophic factor deficiency

eg. Equine Hyperlipidaemia, feline hepatic lipidosis, preg toxaemia
Fat metabolism---> 3 stages

(Patho)
Uptake- FFA---> goes to liver
(inc uptake- accumulation)

Catabolism- FFA---> TG--->lipoproteins--->VLDL
(dec utilisation/ oxidation (Damage))

Secretion- VLDL hydolysed in mm and adipose tissue
(dec protein= dec lipoprotein creation and secretion)
Necrosis- 5 types
Coagulative

Caseous

Liquifactive

Gangrenous

Fat
Causes of Necrosis

Death occurs when...
Toxins, free radicals, hypoxia, trauma

1) Mito irreversibly damaged.
2) Massive CA++ influx due to ATP deplet.
3) Enzymes activated
(eg. phopholipases, ATPases, Proteases, Endonucleases)
Repurfusion injury
Blood supply restored---> inc Ca++ brought to site of damage---> further activation of enzymes
Cellular morphological changes in Necrosis

Nuclear changes
Cytoplasm swollen, eosinophillic, detached

Pyknosis- basophillic, condensed nucleus

Karyorrhexis- fragmentation

Karyolysis- dissolution
Coagulative Necrosis
Cause-

Gross-

Micro-
Due to ischaemia and toxins

Firm and pale

Preservation of basic architecture- no proteolysis
Caseous
Cause- eg

Gross-

Micro-
Bacterial dz- Tuberculosis and caseous lymphandenitis (C.pseudoTB)

Granular, friable, white/cream colour, chronic loss of architecture

Cell coagulation, fragmentation, surrounded by granulomatous reaction
Nuclear and cytoplasmic debris
Mineralisation- calcification
Liquefactive
Causes-

Gross-

Micro-
May follow coag. nec.
Due to bacterial infection + abscess formation in CNS (lipid content high- low CT)

Cavity filled with pus

Enzymatic digestion of cells
PMN cells
Gangrenous- 2 types
Dry- Mumified extremity after ischaemia and coag necrosis

Wet/Gas- Putrefied tissue (from bact. infect.)---> enzymatic liquefaction
Fat Necrosis
Cause-

Gross-

Micro-
Due to- release of pancreatic enzymes
- trauma (eg parturition)

White/cream colour and chalky (Fat+Ca2+---> soap)

Outline of necrotic cells c blue mineral depos
Cholesterol Clefts
Cholesterol xll from dead cells dissolve during fixing to leave clefts
Results of Necrosis (x6)


(-ations)
Inflammation

Disappearance of necrotic cells/debris- phagocytosis

Encapsulation/ replacement/ regeneration

Sequestration- seperation from healthy tissue

Desquamation- sloughing

Dystrophic calcification
Necrosis vs PM changes
Autolysis without inflammation (still loss of structure)

Still have putrefaction- no inflam.
Apoptosis
Phases-

Causes-

Morphology-
initiation-
inflam mediators ---> activation of caspases

Execution-
caspases cause cell death

Causes- mito damage, DNA damage, T cells...

Morphology- cell shrinkage + nuclear fragment./condensation
Membrane retained until the end

NO inflammation
Karyorrhexis

Karyolysis

Pyknosis
Fragmentation of nucleus

Dissolution of nucleus

Condensation of nucleus
5 signs of inflammation
Heat (calor)

Redness (rubor/tubor)

Swelling (tumor)

Pain (dolor)

Loss of function
Inflammation leads to the activation of...
(x5)

And accumulation of...
(x3)
WBCs (leukocytes)
Clotting factors + platelets
Complement factors
Mast cells
fibroblasts

fluids
proteins
Connective tissue inc elastin, collagen, proteoglycans
Chemical mediators of inflammation...
(x7)
Histamines
PGE
leukotrienes
cytokines- (eg. IL-1, TNF IFN)
NO
Compliment
WBCs
Definititions-

Exudation

Exudate

Pus

Transudate

Cytokines

Chemokines

Chemotaxis
Escape of fluids, proteins and cells from BV to tissue

High protein extravascular fluid (SG> 1.020)

Purulent exudate- contains WBC

Low protein extra vascular fluid (SG<1.012)

Soluble proteins which bind to cell and change funct.

Attractant cytokines- induce cell movement

Migration of WBC along chemoattractant gradient
5 stages of inflammation...
Vascular changes

Cellular events

Migration and activation of WBC

Systemic reaction

Repair/ regeneration
Acute inflammation

Causes-
Rapid repsonse to trauma

Physical
Chemical
Infectious
Hypersensitivity
Tissue necrosis
FB
Vascular changes in Acute inflam
(x4)
(1) Coag cascade (intrinsic and extrinsic)

(2) Oedema- dilutes toxins and delivers Ab and enzymes

(3) Activation of endothelium for WBC

(4) Dec blood flow (loss of laminar flow)---> margination of WBC
Causes of oedema in Acute inflam
Hyperaemia (may be a brief constriction then dilation)
---> due to insult or damage related mediators

Inc permeability- endo contraction/ detatch/ damage
--->damage from WBC release of FOS
---> Inc channels prod by VEGF

inc hyrdostatic press. +dec osm. colloid press. ---> Net extravasation
Cellular events
Influx of cells inc WBC and platelets
Circulating cells...
Neutrophils/Heterophils- Phagocytosis
- 6-12hrs

Eosinophils- In parasitic infection +hypersens.
- Release granules and cytokines

Basophils- Similiar to Mast cells
- IgE R present
- Rare

Lymphocytes- T and B

Plasma Cells
Cells in tissue...
Mast Cells
- Degranulate---> release histamine
- Initiate vasc response
- High IgE affinity Rs

Macrophage- phag + APC
- 12hrs+
WBC activation- (Neut., mono., eos.,baso., lympho.)
Cause-

Results-
Complement/ microbes/ cytokine + WBC
--->---> Inc cytolsolic Ca++---> act of enzymes (Protein kinase C and PL a2

Result- expression of adhesion ("homing") molecules on WBC (L selectin and Integrin) and endothelium (P and E selectin)
Sequence of WBC activation/ extravasation...
(x5)
1) Margination

2) Tethering/ rolling (tempory adhesion- req endothelial activation)

3) Adhesion ---> Pavementing
-inc endothelial binding
- Cytoskeletal reorg + GTPases (changes actin)---> inc motility---> allows amoeboid motion

4) Diapedesis/ emigration/ transmigration (along fibrin)

5) Chemotaxis
-exogenous- bacterial products
-endogenous- C5a, chemokines etc.
Phagocytosis
3 stages
1) Recognition- Fc Rs on WBC/ opsonin eg IgG, C3

2) Engulfment
- Actin psuedopods enclose particle
- Phagosome and Lysosome---> Phagolysosome
---> dec pH +activates enzymes +ROS- oxidative burst
(defect = Chediak-Higashi syndrome (persians))

3) Killing and degredation
- O2 dep.---> free radicals
- O2 independ. ---> NO, BPI (increase perm.), MBP

- Degredation via hydrolases
Byproducts of WBC activity

"collateral damage"
Enzymes, ROS and eicosanoids released
---> cause tissue damage in surrounding cells
--->amplify effects of injury (or create injury- RA)

-Cytokines prod from activation---> MP chemotaxis

-Prod of arachodonic acid metabolites (eicosanoids)
PL---(PLa2)---> AracAcid---(LOX)---> Lipoxin+Leukotrienes
---(COX)---> PGE + thromboxane

(PLa2 inhib by corticosteroids)
Plasma bourne chemical mediators...
Complement

Coagulation cascade- thrombin activation
end point ---> converts fibrinogen--->fibrin
- intrinsic and extrinsic pathways

Kinin (Hageman factor)
Bradykinin---> BV dilation + inc perm., Inc AracAcid metabolite production., hyperalgesia

Fibrinolytic system- (activated by hageman factor)
---> generates Plasmin---> cleaves C3 (activates Hageman factor (XII))
--->fibrin degredation products are chemotactic
Complement-
What-

Cause-

Pathways and stimuli-

Important molecules-

end point
-20 plasma proteins secreted by liver as precursors

- Cause
- Vascular change---> BV dil., Inc perm.
- Opsonisation
- Innate and adaptive immunity

Classical/lectin-
Ab and Lectin binding to bacterial proteins

Alternative-
Microbes

Important-
C3b---> opsonin
C5a---> chemotactic and activates LOX pathway

End point- MAC ---> lyse bacterial and fungal walls
Pain
Receptors-
Mechanoreceptors- sense swelling

Thermoreceptors- detect Inc temp.

Pain R- activated by PGE2, histamine and bradykinin
5 types of acute inflammation
1) Serous

2) Catarrhal/ mucous

3) Fibrinous

4) Suppurative/ purulent

5) Haemorrhagic
Serous inflammation
- Relatively mild

- Thin, clear/yellowy watery transudate/ fluid filled vesicles

-eg. Early pneumonia/ blisters/ effusions/ oedema/ urticaria
Catarrhal/ mucous inflammation
- Caused by low virulence microbes

- Yellow/green/grey mucoid discharge

- +/- surface epithelia in exudate

- +/- pus (mucopurulent)
Fibrinous inflammation
- Inc vascular permeability---> loss of fibrin into ECS
---> fibrinous exudate

-Gross
- Yellow flecks/ strands in body cavity effusions
- Yellow/red coating on peritoneal/visceral surfaces (mucous and serous membranes)

-Fibrin may be voided as cast/ phagocytosed or fibrinolysed/ become organised

eg. Traumatic pericarditis
Suppurative/ purulent
-Usually of bacterial origin (esp Strep or Staph)

- Yellow/ green/ grey viscous liquid- high protein conc

- +++ neutrophils, necrotic cells, bacteria, metabolites

- Accomp. by immune resp. ---> Ab and fever

- Retained pus ---> endotoxaemia/ septicaemia/ bacteraemia

- May present as abscess- focal collection of pus

- (Can also occur with chronic inflam)
Haemorrhagic inflammation
-Haemorrhagic exudate due to v. virulent organisms/ toxins

-Tissues appear red/black, may have viscous (jam- like) exudate

- e.g Anthrax
Ulceration
Definition-

Causes-
-Local defect/ excavation on surface of organ or tissue due to sloughing of necrotic inflam tissue which breaches muscularis mucosa or BM.

Diptheritic membrane formation
- pseudomembrane of fibrin (prod by fibroblasts), inflammatory cells (MPs) and necrotic debris.
Erosion
Definition-

Causes-
- Loss of epi layers but muscularis mucosa and BM are intact

- Fibrinous exudate + inflam.
Termination of acute inflam
-Expiry of short term mediators

- Apoptosis of neutrophils

- Leukotrienes---> lipoxins (anti-inflam)

-Anti-inflam mediators released by MPs eg TGFb
Outcomes of acute inflammation
(x5)
1) Complete resolution- if minimal damage has ensued

2) Healing by fibrosis- can lead to loss of function

3) Abscess formation
(which)
4) May become sterile- pus is resorbed and reorganised

5) Progression to Chronic inflam.
Abscess
Define-

Morphology-
- A focal collection of purulent inflammatory tissue

- Central necrotic area
- Surrounded by neutrophils
- outer layer of fibrosis/ fibroplasia
Response of acute inflammation...
(x5)
Systemic inflam. resp. (SIRs)
- Pyrexia
-Endog. (IL1) and exog. pyrogens (bact)---> Inc temp

- PGE synth in hypothalamus

- Plasma protein production and release moderated
- eg C reactive Protein
fibrinogen (rouleaux formation)
serum amyloid A protein (2o amyloid. if prolonged)
Other Acute phase proteins
---> Inc HR, BP, T etc

- Leukocytosis (left shift due to Inc prod of precursors)
or
- Leukocytopaenia- If overwhelming infect.

- Metal ions
-Dec plasma Fe, Zn but Inc Cu

Usually of benefit to host, otherwise---> Septic Shock occurs
Clinical signs of acute inflammation
(x5)
Dec. sweating

Inc shivering

Anorexia

Somnolence

Malaise
Chronic inflammation
-Prolonged duration of active inflam., tissue destruction and repair occuring simult.
-Mononuclear cell infiltrate + accum.
-MP, lympho, plasma cells
-Tissue destruction
-healing by fibrosis and angiogenesis

-May follow acute or be chronic from the off.

- Occurs when host cannot resolve/remove insult
(Persistant (-eg. TB- delayed hypersensitivity) or autoimmune)
Chronic inflam. - Morphology

Gross-

Micro-
-Often grey/cream, frim, nodular or pitted surface

- Micro depends on cellular infiltrate- predom MP
Monocellular infiltration- 4 stages
1) Recruitment- chemokines, GF, cellular debris

2) Activation

3) Division

4) Immobilisation- chemokines, oxidised lipids
Monocyte Activation
- Activated by cytokines eg IFN/ endotoxins/ chemical mediators

-monocytes---> MP by fusion- become multinucleated

- Inc size, may become epithelioid (adapted for inc protein secretion)
MP funct.
(x4)
- Eliminate injurious agent

- Initiate repair - fibrosis +angiogenesis
(stim by hypoxia, low pH, high lactate---> GF released)

- Cause influx of other cells

- Cause tissue injury in chronic inflam
(enzymes, toxic o2 metab., chem fact., coag fact. etc)
Chronic inflam-
recruitment-
-Recruited by cytokines and APCs presenting to CD4+ T cells.

- Bidirectional interaction of lympho + MPs

- Act. T lymph---> IFNg---> Act. MP
- Act MP---> IL12 or Ag ---> Act T lymph
- Both prod TNF and IL
Chronic inflam-
Other cells and funct.-
- Plasma cells- from B cells

- Eosinophils- med by IgE

- Mast cells - prod cytokines ---> fibrosis + remod.
- (acute inflam---> type 1 HS)

- Platelets- trapped in thrombi
- release GF---> stim gran. tiss

- Fibroblasts- make collagen/ ECM ---> make fibrous tiss and scars

- Myofibroblasts- contract wound during healing

- Endo. cells- angiogen/ neovasc.

- Neutrophils- med. by T cells/ MPs/persistent microbes
Granulomatous inflam.
Morphology-

Seen in-
- Presents as mass
- Can be solid or have purulent/necrotic center
- Accum of activated, often epithelioid, MP around
- Then layer of lymph., plasma Cs, MPs and fibrous tiss.
- Diffuse or nodular (organised)
- May be mineralised
-May have fibrous capsule

-Seen in
-immune med. infects eg. TB
- non immune med. eg FB
-idiopathic
Granuloma Types
- FB granuloma- Low turnover as little MP death, FB covered in MP- try to phag. (eg sutures)

- Microbe related granuloma - High turnover, MP present to T cells. (eg. type 4 HS)

- Eosinophillic granuloma- nuclear material, lots of MP and eosinophils (eg bite reaction)
Regeneration
Define

Requirements
- Renewal or compensatory growth

- Req intact CT scaffold (ECM)

- Occurs as nodules or as normal architecture

- Capacity is tissue dep.- high= CT, BV, med= cart., tendons, low= nephrons, neurons
Cell Growth Cycle-
Cycle-

Types-
G1--CP--> S (synth) --->G2--CP--M (mitosis)---> G1--->...

G1---> G0 (resting phases)

- Permenant cells- eg. neurons- no cycle

- Quintescant/ stable- eg hepat.- in G0 but can progess

- Labile- eg. epi -constant turnover
Healing-
Define-

When-

Fibrosis-
- Combo of regen. and fibrosis---> scarring

- Occurs with damage to ECM- eg necrosis, or with abund. fibrinous exudate- organised

- fibrosis occurs after 24hrs inflam
- if no resolution then prolif of fibroblasts and endo cells
--->organisation ---> Granulation tiss., Angio+neovasc.
Granulation tissue
Gross-

Micro-

Progression-
Gross- roughen/ granular moist pink tissue above level of skin

- Capillary loops perp. to skin, fibroblasts parallel- "basketweave"
- No nn---> bleeds lots

-Initially very vasc. c MP, lympho and few fibroblasts

- Later- less vasc. (capillaries atrophy), more fibroblasts, dec inflam cells

- Finally GT replaced by fibrous tiss.- require degred. of ECM by MMP first
Angiogenesis requirements-
(x5)
1) Mobilisation of endo precursor cells

2) Proteolysis of ECM

3) Migration and prolif. of cells

4) Lumen formation

5) Maturation and inhib of growth
Fibroplasia-
- Plasma proteins- scaffold for ECM
-eg. fibrinogen

-Collagen depo.

-Fibroblast migration- stim by GF, IL1, TNF
First intention healing
Type of wound-

Sequence of events-
(x8)
- Clean, uninfect. surgical incisions

1) Fibrin plug- scab

2) Clot removed by Neutro.

3) Epithelialisation-
- Desmosomes dissolved, actin prod,
- Prolif. and migr. of epi.---> BM deposited
- Epi cells fuse midline (quicker if moist and well oxygenated)

4) Day 3- MP replace neutro.

5) Day 5- Granulation tissue and collagen

6) Week 2- Inflam gone, inc collagen, BV regress.

7) Tensile strength returns

8) Collagen scar

Adnexae destroyed are permenantly lost
2nd Intention healing-
Type of wound-

Sequence of events-
(x6)
- More extensive loss of cells and tissue ---> larger fibrin clot req. and inc inflam.

1) Fibrin clot

2) Granulation tiss. form.

3) Epi migration, fibro prolif., collagen prod.

4) Wound contraction- myofibroblasts (actin)

5) Fibrous scar and collagenous remodelling

6) Epi and keratin hyperplasia

-(wound strength due to x-links and fibre size
Delays in wound healing
(x7)
- Nutrition- protein/ vit C etc

- Mechanical- lack of immob.

- Vasc inadequacies

- Other dz

- Glucocorticoids- inhibit MMP

- Size of wound

- Infection/ necrosis/ haem./ FB etc
Complications of wound healing
(x3)
1) Inadequate granulation tiss./ scar form.

2) Contractures- excessive contr.

3) Excess fibrosis + angio from persist. stim.---> proud flesh
Bone # Healing
1) # ---> Haemorrhage ---> Haematoma + inflam + bone necrosis (empty lacuna)

2) Organised haematoma= pro-callus (soft tiss.)

3) Cytokine release---> stim osteoprogenitor cells (eg osteo, chondro and fibroblasts)
--->Remodelling of # ends

4) Deposit. of woven (immature) bone +/- cart. (inc cart with dec o2 tension)- Week 3- max callous girth

5) New cart. --(endochondrial ossif.)--> Trabecular bone
(if gap <1mm---> trab. bone)
(if gap >1mm---> woven bone)

6a) 1o callus- Trabec. join up (no woven bone)
6b) 2o callus- Mineralisation of woven bone---> replaced with lamellar trab. bone

7) Repair req direct osteonal bridging, no callus. Further remodelling due to stress.
Abnormal/ Delayed # repair
-# is comminuted/ displaced

- # is inadequately immob.

- Infect/ dz/ patho #

- Dietary def. eg Ca++, P, Vitamins

- Abnormal Callous (made of FT/ cart.)

- Non-union

- False joint formation
Vascular Changes and Circulatory Disturbances
- Oedema

- Hyperaemia

- Congestion
Oedema
Morph-

Mech-
- Controlled by starling's law- Filtration vs. Absorption

- Morph- excess clear fluid

- Mech
-Inc vasc. perm.
- Inc hydrostatic fluid
- Dec osmotic press. - Loss of protein
- Lymphatic obstruct. eg. lymphadenitis
- Na+ retention eg. renal failure.
Hyperaemia
- Active inc. inflow of blood due to v.d.

- Phys.- assoc c inflam due to heat
Congestion
- Passive

- Stasis of blood---> low o2---> hypoxia---> cell damage

- Hypostatic congestion- due to gravity eg recumbancy
Haemostasis
Components-
- Vasc. wall- endothelium
- Anti-thrombotic- bloacks platelet adhesion, interfers c coag cascade
- Pro-thrombotic- vasoconstrict., adhesion etc.

- Platelets- Adhere to ECM via vWF bridge + become activated
- secrete granules containing ADP and Ca++
- Expose PL complexes

-Coag cascade
- Prothrombin ---> Thrombin
Fibrinogen ---> Fibrin
Normal Haemostasis
Sequence-
1) Initial injury to vessel wall

2) Transient v.c (neuro reaction + local factors)

3) 1o Haem - Plug formation
( Platelet 1) adhesion, 2) shape change, 3) Granule release, 4) Recruitment, 5) Aggregation)

4) 2o haem- Coag cascade
( 1)Tissue factor, 2) PL complex expression, 3) Thrombin activation, 4) Fibrin polym.)

5) Regulated by tissue 1) plasminogen activator, 2) Thrombomodulin- blocks coag cascade
Haemorrhage
Forms-

Causes-
- Petechial- Pin point haem.

- Ecchymoses- foci <3cm

- Haematoma- tumour like enlargement

- Haemorrhagic disastheses- haem from insignif. insult

Causes
- Clotting fail.
- Trauma
- Destruct. of vessel
- Toxins
- Infectious agent
- Defic.- eg. Vit C, K, E
Thrombosis
Define-

Causes-

Diff. from PM clot-
- From dysregulation of haemostasis

- Predisp. by
- Endo injury
- Stasis/ turbulence
- Hypercoag- genetic vs. acquired

- All have a point of attachment unlike PM clot.

- PM clot= gelatinous c dark red area + yellow supernatent where cells have dropped

- May break off---> Embolus
Types of Thrombi-
-Arterial/ cardiac chamber thrombus
- Gross- friable, red/ grey, roughened surface
- Micro- laminated- lines of Zahn- grey=platelets, red=RBCs + fibrin

-Venous (often in areas of stasis)
- Gross- Extend in direction of BF
- Micro- Flocculent, amorphous eosinophillic mush- no lines

- Heart valve clot- (esp LAV) occurs with valve damage
Thrombus sequalae-

Consequences-
- Dissolution- removed by fibrinolysis
- Propogation- accum. fibrin and platelets
- Embolism
- Organisation and recanalisation

- Obstruction
- Embolism
Embolisms-
- Can be
- Solid- bone #, fat, thrombus
- Liquid
- Gas- Air
- Bacteria
Carried by blood
Infarction
Define-

Gross-

Consequences-
- Area of ichaemic necrosis (coag (liquefactive in brain)) caused by occlusion of BV

- Gross- wedge shaped
- Red- haemorrhagic- vessel damage
- White- anaemic- from art. occlusion/ haemolysis/ Pressure

- Consequences
- Depends on
- Nature of BS
- Rate of occl. dev.
- Vuln. of tiss. to hypox.
- o2 conc in blood
Amyloid deposition morphology-
-Amyloid- (rare) insoluble proteinaceous fibrils folded abnormally into beta pleated sheets,

- Pink with Congo Red stain

- May disrupt function/ compress surrounding tissues

- Gross- firm, pale/white opaque, lard like
- May appaear as black dots
- Green under polarised light

- Micro- Hyaline, glassy, eosin. c H&E
Classification
- Classification-
-Generalised- kidneys, liver, spleen...
-1o- B/plasma C dyscrasia (cancer)- Bence Jones test
-2o- Assoc chronic inflam- serum amyloid A proteins
- Senilei naturally occuring c age
- Hereditary- eg abbessinians

-Localised- Cardiac/ cerebral (Alzheimers)/ pancreas
Calcification
Types-
- Dystrophic- in degen. + necro. tiss.- unrelated to blood

- Gross- white/grey honeycombed, gritty, hard to cut

- Seen on degen invert. discs/ old TB lesions

- Micro- Basophillic/ purple/ amorphous

- Can be intra/extra cellular

- Confirm with Alizarin red or Von Kossa tech.



- Metastatic- persistently high blood conc---> ppt on organelles
- Affects elastin in BV, trachea, heart valves, stomach and skin
- Due to kidney failure/ excess Vit D/ hyperPT
Calcinosis cutis
Define-

Cause-

Gross-
- Ca++ depos. in dermis and sub cutis

- Cause
- Dystrophic calcification- due to cushings
- Metastatic
- Iatrogenic
- Idiopathic- generalised vs localised (Calcinosis circumscripta)

-Gross
- Firm plaques under/on surface of skin
Calcinosis Circumscripta-
Location-

Gross-

Cause-
- Uncommon lesion in dogs and Horses

- Affects skin, tongue, soft tissue on back.

- Raised chalky/ putty-like/ gritty nodules seperated by CT
- Hyperplastic epithelium

-Caused by dystroph. Ca++ on damaged coll. at sites of trauma/ sutures
Uric acid/ urates
Define-

Gross-

Location-

Pathology-
- Xlls---> end point of purine metab. depos. in tiss. (Gout)

- Gross
- Articular ---> White, chalky nodules
- Serous ---> white/ grey layer

- Visceral serous deposits most common- esp kidneys

- FB reaction to xlls ---> acute and chronic inflam.
Intracellular accum.
Define-
-Normal cellular constituents in excess (glycogen/ TG/Chol/ PL etc.)
Or
- Abnormal endog./ exog. substances

-Range- Harmless---> Toxic// Temp.---> Permenant
Haemosiderin
Define-

Causes of haemosiderosis-

Micro-

Path-
- Endogenous pigment derived from haemoglobin
- = Accum. of micelles (Fe+ apoferritin)
-Part of Fe storage pool

- Present normally in MP (haemosideroP) of spleen and bone marrow.
- Excess present in haem./ bruising due to haemolysis

-Haemosiderosis-
- occurs due to systemic excess of Fe---> Haemo. depos.
- Also H.A., chronic pass. congest.---> "heart failure cells" in lungs

- Micro- Golden brown xlline or granular material
- Use Perl's prussian blue

Path- non harmful but indicator of haem.
(haemoglobin toxin to renal tubules ---> black)
Bile Pigments
Source-
- Bilirubin prod. after seperation of haem+ Fe/Globin

- Excess= jaundice/icterus
- Pre hepatic- haemolysis
- Hepatic- hepatitis, liver degen.
- Post hepatic- choleostasis
Other pigments
Lipofuscin-

Ceroid-

Melanin-
Lipofuscin- "Aging pigment"- non harmful
- due to free radical damage (ROS)
- Lipid + protein
- Prominent in slowly dividing cells
- Stained by Schmorl's technique

- Ceroid- Pathological version of lipofuscin
- From severe malnutrition/ Vit E def./ high unsat. fat/irradiation

- Melanin- Brown/ black pigment
- Melanosis- normal
- Melanoma/cytoma- melanocyte/blast tumour
- Path. depo in skin during chronic inflam./ cushings
Carbon

Others
- Common- from air pollution
- Anthracosis- collection in lungs/ LNs

- Pseudomonas
-Some fungi
Lysosomal storage dz
- Lysosome= 1o disposal + recycling centre
- Catabolise cellular and EC macromolecules for use in cell

-LSdz- rare- genetic basis- idiopathic/ acquired
- Lack enzymes/ transport of enzymes---> accum. of catabolites
Cellular aging
- Progressive decline in prolif. capacity

-Decline in functions-
- Oxidative phosp.
- Synth of NAs and protein
- Repair

- limited number of replications per cell
- Telomere shortening
- Genetics
-Accum of metabolites
Review- Acute vs Chronic inflam

Cause-

Major Cell types-

1o mediators-

Duration-

Outcomes-
-Acute- Pathogens or injury
-Chronic- Acute inflam, pathogens, FBs, auto-immune

- Acute- Neutro., eosino., baso., monocytes and MP
- Chronic- MN cells- MP, mono., lymph., plasma C, Fibro.

- Acute- Vasoactive peptides + eicosanoids
- Chronic- IFNg, cytokines, GF, ROS, enzymes

- Acute- Few days
- Chronic- Months, years

- Acute- Resolution, abscess, chronic inflam
- Chronic- Tiss. destruction, fibrosis, necrosis, resolution.