1. G1 (presynthetic)

2. S (DNA synthesis)

3. G2 (premitotic)

4. M (mitotic)

>resting cells are in the G0 phase, then they enter the cell cycle they enter at the G1 stage

cells are not capable of division, they are nondividing, they are also called permenant cells

>example: neurons, muscles cells of heart and skeletal muscle...  they have left the cell cycle and do not reenter

>short lived, incapable of replication

LABILE

>have stem cells that proliferate and replace the mature or terminally differentiated cells

-present in a resting state

-when injured have cells that are able to divide

>ex: liver, kidney, pancreas, mesenchymal cells (fibroblasts/sm muscle), vascular endothelial cells and resting lymphocytes

-epidermal  (EGF)

-transforming (TGF beta)

-insulin like (IGF)

>have major roles in controlling cell proliferation and differentiation

>there are both activators and inhibitors of each part of cell cycle, operate to stop cycle at transition phases especially b.w. G1 and S (CHECKPOINTS)

cell swelling

aka hydropic degeneration

-most common manisfestation of cell injury

-cells swell bc they cannot control entry or loss of water

-lose ability to maintain ions such as N and K bc of membrane damage

or fatty change

-manisfestation of type of reversible injury

-occurs in those organs where fat is metabolized...especially the liver!

death from cell swelling

>enzymes from lysosomes leak in the cell and degrade nuclear and cytoplasmic components...this allows detection of tissue specific injury by using serum ->creatine kinase is released from damaged heart muscle and is used to detect necrosis of heart muscle in a heart attack

death by apoptosis

morphologically

death by apoptosis

biochemically

apoptosis is the result of biochemical pathways that involve caspase induced destruction of proteins

>ex: coagulative necrosis is a morphological descriptor, describes what happens when cells die and remain same size  ->meat in super market

freezing usually occurs relatively slowly and large ice crystals form within the cells

-these ice crystals have the same effect as a series of knives, cut and lacerate the normal cytological structures

-as cell begins to thaw frozen cells with their disrupted membranes will break and undergo hydropic degeneration bc of the breeches in the cell membrane

>determines the movement of fluid in the capillary bed

>blood pressure = peripheral resistance x cardiac output

>it's low, but must be maintained in a narrow range to ensure a net movement of fluid from the blood vasculature into the tissues

>movement of fluid into extracellular compartment around tissue cells will increase the oncotic pressure within the blood vascular system

>proteins such as ALBUMIN create this oncotic pressure

>as blood moves from arterial to venous, hydrostatic pressure is overcome by the draw of oncotic pressure

>increas in oncotic pressure results in a net flow of water back into the vascular system

>ensures a continuous movement of fluid through and flushing of the extravascular space

>excessive fluid in extravascular space is removed by a specialized vascular system called lymphatic system

occurs when there are alterations to the forces at the venous end of the capillary, either with a reduction in oncotic pressure or an increase in venous hydrostatic pressure

oncotic pressure in the intravascular space is reduced and there is less attraction for fluid to reenter the blood vascular system

>ex: kwashiorkor, severly malnourished children with ascites

active process where the precapillary sphincter opens to allow a greater amount of into the capillary beds of a tissue

>ex: blushing

-very dramatic vascular disturbance

-means release of blood or RBCs from the vascular system

>most extrememe form of haemorrhage

>swelling (oma) of blood

>smaller haemorrhaging

>RBCs move out of capillaries bc of widening of the gaps bw endothelial cells

>smallest haemorrhage

>pinpoint haemorrhaging

>variant bw petecia and haemotoma

>usually a whole series of petecial haemorrhages that appear as though blood was wiped on the tissue, 'paintbrush haemorrhaging'

>endothelial cells; very active, normally anticoagulative

>platelets; cell membrane bound fragments of the cytoplasm of megakaryocytes of the bone marrow, recognize breaches in endothelial layer, adhere to collagen/extracellular matrix, secrete thromboxane which stimulates platelet function

>coagulation cascade; series of proteins found in blood, mostly produced by liver

Normal Haemostasis

>at site of vascular injury

-initial vasoconstriction induced by local nerve reflex and augmented by chemical vasocontrictors such as endothelin

-platelts adhere to exposed extracellula matrix, undergo a shape change and recruit other platelets to form a primary plug

-tissue factor activates coagulation cascade

-produce fibrin mesh that forms secondary plug

-platelets and fibrin combine to form permanent plug

-regulatory factors ensure plug does not expand to form large thrombus

DIC

>dissmeinated intravascular coagulation

clustering/aggregation of a substance within the blood stream

>emboli can be thrombi

>the bends; emboli of bubbles of gas

-occurs in heart failure

-heart function greatly reduced

>aka polynorphonuclear granulocyte

>short-lived, rapidly mobilized

>monocyte, histiocyte, microglial cell, kupffer cell, mesangial cell, langerhans cell

>slower to respond, longer life span, links innate and adaptive immunity through antigen presentation

-substances that are recognized by cells of the adaptive immune system as being either 'self' or 'foreign'

 >Ag specific immune response is lead by lymohocytes

-replicate in response to Ag exposure producing a clone (epitope) of Ag responsive cells

-clonal proliferation increases the number of lyphocytes that recognize the same epitope on subsequent exposure >>more rapid and enhanced (memory)

lymph+Ag+stim. envt. >proliferation/clones of epitopes/sensitive cells >>efector cells and memory cells

vertical >from mother before or at birth

horizontal > from one to another after birth

...some are contagious; transmitted directly to another host of the same species

prion >infectious protein

viruses >obligate intracellular

chlamydiae >ob intra

rickettsiae >ob intra

bacteria >intracellular/extracellular

fungi >intra/extra

protozoa >intra/extra

helminths >intra/extra

mycoplasma >extracellular

arthropods >extracellular

-mobile genetic elements

-multiply in cells

-have genome for RNA and DNA, protective protein coat/capsid that allows them to pass from one cell to another

-transmitted via direct/indirect contact

-viruses cause damage by entering a host cell and replicating at its expense

-have  tropism for particular cell bc of specific receptor on the cell

-may inhibit hose cell DNA/RNA/protein synthesis

-may damage cell membrane or cell lysis (due to replication within cell)

-some integrate proteins w/in cell mem. which inscites immune attack by host >causes lysis, or may activate cell

-after infection, body responds with inflammation, Ab formtn and or cellular immunity

-in some cases interferon is formed

-protein produced by virus-infected cell

-prevents viral reproduction in neighbouring cells

-avoidance (quarantine)

-acquisition of immunity by vaccination >usually given before exposure to an agent by can be given after exposure if incubation period is long or disease is really serious

-tx with antiviral drugs is limited by the toxicity of most drugs and by their limited range of effectiveness

-interferon, only mucosal surfaces cz too toxic

-acyclovir inhibits DNA syntheses

-azidothymidine inhibits revers transcriptase of HIV

1. human herpesvirus 1 >cold sore

2. human herpesvirus 2 >genital herpes

3. vaicella zoster >chicken pox, shingles

4. cytomegalovirus >CMV

5. human herpesvirus 6>roseloa infantum

6. epstein barr virus >western world infectious mononucleosis; africa, burkitts lymphoma

-seperated into two groups; Gram +ve and Gram -ve

Gram +ve >have thick cell wall

Gram -ve >thin wall and an outer membrane of phospholipid, lipopolysaccharide and protein

-rapid multiplication (competes with the host for nutrients, the production of exotoxins/endotoxins and by inducing host response)

produced by bacteria and released into the environment

-toxins may be waste products or factors that assist the organism to survive, reproduce or be carried to the next host

structural components of the cell walls of Gram -ve bacteria

-complex of lipopolysaccharide and protein

-potent activator or macrophages and stimulates the production of IL-1 and TNF

primary response >neutrophil, usually forming pus (pyo)

-purulent or suppurative and in some cases granulomatous, inflammation are the main ways that the body responds

-complement macrophages and humoral (Ab) and cell immunity assist in removal of bacteria

-avoidance and sanitation

-active immunity >stimulated by vaccination (often with toxoids; like toxins...they are antigenic but not pathogenic)

toxoids >made from exotoxin, antitoxin (or antiserum) can be given to prevent disease in an exposed individual

antibiotics >antibacterial drugs derived from microorganisms

-synthetic antimicrobials are called chemotherapeutic agents

-they work in two main ways: bacteriocidal,kill bacteria/bacterostatic, stop them from multiplying

is change of cells of one tissue type to another

-occurs bc of injury or excessive stimulation

abnormal development or growth of cells or tissues

-often preneoplastic change and is therefore a prelude to neoplasia

'net growth'

-at the heart of neoplasia is uncontrolled growth, 'the presence of abnormal growth regulatory mechanisms'

-have genetic and epigenetic changes that are passed onto future generations of cells so that they are no longer responsive to the normal control of growth

-despite genetic change, avoid checkpoints in the normal cell cycle...causing perpetual cell cycle

-act independently

-type of neoplasia

-'crab', refers to the affects of some neoplasms in the body (clawing at the internal organs)

-commonly used to denote any neoplastic disease, more often a malignant one

-cancer also means malignant epethelial neoplasia or carcinoma

-means swelling

-common usage is for neoplasia that is benign

demarcation >poor

invasion >yes

rate of growth >high

differentiation and anaplasia >poor

pleomorphism >marked

metastasis >yes

mitosis per high power field >high

spread of a disease process from one location to another without direct connection between them

-occurs bw surfaces and cavities, via lymphatics, haematogenously and by contact

gastric erosion

-ulcer

gastric erosion is the loss of gastric mucosa bc of death of epithelium

-ulcer is deep 'erosion' that penetrates muscularis mucosa

mature eneterocytes secrete what for what?

enzymes for the final breakdown of food

>this includes dipeptidases/disaccharrides for the absorption of food

...fat that is processed, forms chylomicrons, released into lymphatics

what is diarrhea?

what are the mechanisms of diarrheal disease?

>presence of water in feces in relative excess in proportion to the fecal dry matter

>secretory, malabsorptive, exudative, osmotic and deranged motility

-occurs when secretion of fluid by immature cells is in excess of the absorption by mature cells

-happens in cholera, toxin causes increase secretion of fluid

-occurs when there is a loss of mature cells so absorption can't occur

-rotavirus

-complete destruction of villi/crypt and exudation of plasma proteins through eroded surface

-salmonellosis or radiomimetic injury

-osmotically active substances are [resent on the lumen

-MgSO4 or seawater ingestion, lactose intolerance

Traveler's Diarrhoea

-Agents

-Prevention

-Tx

agents >enterotoxigenic escherichia. coli, shigella sp, campylobacter jejuni ...passage of at lease 3 unformed stools in 24 hour, nausea, vomiting, abdominal pain/cramps, fecal urgency, tenesmus or passage of bloody stool

prevention >depends on amt of time spent in new area, long = natural immunity, short = dietary restriction/chemoprophylaxis are alternatives

tx >fluids/electrolytes, ex: flavoured mineral water and saline crackers

production of the cells of the blood

-erythropoiesis = production of erythrocytes

-granulocytopoiesis = production of granulocytes

-thrombopoiesis = production of platelets

in the spleen

...granulocytes exit to the tissues

...lymphocytes home to lymph nodes/spleen/other lymphoid tissue/form long lived circulating pool

PCV or hematocrit

-what does this do?

-evaulates erythrocytes

-red cell mass in comparison to fluid in blood

young red cells are larger than older cells and have more RNA in cytoplasm, stain blue, vary in colour (polychromasia)

-detect blood doping by looking at avg age or red cells

-transfused cells age prematurely, sm mature cells

or 'responsive'

-many young red cells, indicates release from BM

ex: haemolysis, loss of red cells

-reduced PCV, RBC, Hb

-increased numbers of young red cells, presence of polychromasia and reticulocytes 

increase in number of red cells

>caused by dehydration, situations where there is increased erythropoietin secretion, ....hypoxemic conditions predominate and include aerobic training (esp at high altitude), heart/lung diseases 

a left shift.... indicates a marrow response to infection or  death of tissue

-leukocytosis

-neutrophilia 

-left shift

-dramatic or marked leukocytosis, number of neoplastic leukocytes increase

-damage the alveoli or the alveolar walls

-reduction of the functional vol and elasticity of the lung = increase effort of breathing

-cause thickening of the barrier bw the alveolar air and blood (results in poor oxygen exchange)