Pathophysiology curriculum in a simple way

1. Cell Injury Types
Failure of
Na+ pump
sodium ions will accumulate inside the cell
gain of water&cell swelling(hydropic change)
due to
Decreased synthesis of ATP by the mitochondria
Specific injury of ion pumps on the cell membrane by
Ouabain (a drug used in small doses to treat heart failure).
Damage of the
cell membrane
influx of calcium into the cell.
Ca+2 damagemitochondria
due to
Bacterial toxins
Chemical poisons
Common in
highly specialized parenchymatous cells
epithelium ofkindly&liver cells
Reversible
Pathogenesis
seen in
chicken pox and small pox
Liver cells in viral hepatitis
renal tubular epithelium in hypo-kalemia
islets of Langerhans in early diabetes mellitus
Irreversible
(Necrosis)
Morphology
Cytoplasmic
change
Nuclear changes
(light microscope)
ultrastructural changes
(Electron microscopic)
homogeneous or granular cytoplasm
more eosin than normal
due to
loss of
RNA
cytoplasmic basophilia
increased binding of
eosin to denatured proteins
Shrinkage
increased staining with haematoxylin(pyknosis)
Fragmentation into small bodies(karyorrhexis)
Clumping of chromatin within nucleus
followed by its disappearance.
Fragmentation of organelles
followed by their disappearance

2. Types of necrosis
Coagulative
seen in kidney, heart and spleen
necrotic area pale yellow, opaque, swollen and firm
Microscopically
All cellular details are lost
the outline of the tissue is preserved.
manifestations of acute inflammation in surrounding tissues.
Liquefactive
seen in
the central nervous system(CNS)
due to its high lipid content
the centers of pyogenic abscess and amoebiasis.
necrotic tissue
Causeous
(caseation)
Fat
necrotic tissue
necrotic tissue
seen in
seen in
completely liquefied into a turbid fluid
soon absorbed to leave an empty space
tuberculous lesions.
partially liquefied
yellowish-grey,creamy material
resembling cream cheese or casein
Microscopically
general architecture is preserved
both the cellular details and the general architecture are totally lost
homogeneous or granular, structureless,eosinophilic appearance
the female breast
in the omental and mesenteric fat in acute haemorrhagic pancreatitis.
(traumatic fat necrosis)
(enzymatic fat necrosis) the action of pancreatic lipase on the neutral fat
opaque white
Microscopically
cloudy
surrounded by
chronic inflammatory cells
foamy histiocytes
foreign body
giant cells
lead to the formation of a palpable mass in the breast
often clinically mistaken for cancer
may undergo pathological calcification.

4. Irreversible(Apoptosis)
Programmed cell death
programmed obsolescence
chromatin condensation
characterized by
shrinkage of cell volume
an energy dependent process
The chromatin is broken down in a regular fashion
shed from free surfaces
phagocytosed to form apoptotic bodies
The dead cell breaks
into fragments
has a unique morphology
does not elicit an inflammatory response
initiation of apoptosis is regulated by growth factors
physiologic
endometrial cell loss during menstruation
removal of the inter-digital webs during embryologic
development of toes and fingers.
pathologic
Tissues undergoing atrophy
Irradiated tissues
Tissues injured by cytotoxic T lymphocytes
Tumors
Viral infections viral hepatitis
acidophil
Councilman Bodies
in necrosis,groups of cells are killed, But apoptosis tends to affect single cell

6. Cellular disorders
decrease or increases in
the mass of the tissue
Atrophy
Hypertrophy
Abnormal
growth
a decrease in the size of tissue
increase in the size of tissue
Causes
Physiologic
Pathologic
Skeletal muscle hypertrophy in athletes.
uterine muscle hypertrophy in pregnancy
Left ventricular hypertrophy I hypertension
Hypertrophy of one kidney due to
removal of the other kidney
Hyperplasia
increase in the size of an organ due to
increased numbers of cells,
It occurs in labile and stable cells
with or without decrease in the number
Causes
Pathologic
due to effect of hormones
Endometrial hyperplasia
Cystic mammary hyperplasia
(fibrocystic disease of the breast)
Thyroid hyperplasia
(Grave's disease)
increase stimulation of thyroid
stimulating hormone (TSH)
increased estrogen stimulation
particularly when it is not opposed by
progesterone secretion
e.g. near the menopause .
Abnormal
differentiation
Metaplasia
replacement of one normal adult cell type by a different adult
(fully differentiated) cell types
The alteration does not cross
the histogenetic boundaries.
a response to chronic inflammation.
Abnormal
maturation
Epithelial
dysplasia
an abnormality of both
differentiation & maturation
occur in
□ Cervix, vagina and vulva.
□ Larynx.
□ Urinary bladder.
□ Large intestine in ulcerative colitis or adenomas.
Physiologic breast feeding
Bone marrow due to RBCs distrucyion
due to decrease in the size of individual cells
due to Increase in the size of individual cells
Lymph node due to infection

7. Healing
Types
Composition
Capillaries
budding from the
undamaged vessels
the capillary buds are solid
then become canalized
develop a lumen
Organization
granulation(scar)
tissue formation
angiogenesis
neovasculariztion
blood flows
Fibroblasts
from activation of fibrocytes
appear as large plump cells
Initially
mature collagen synthesis
produce proteoglycans
(ground substance of connective tissue)
Macrophages
(migrating
monocytes)
Phagocytose
cell debris
fibrin
RBCs
secretion of
proteolyic enzymes
collagenase
elastase
Clearance of dead tissue
secrete
fibronectin
prostaglandins
Fate
With healing
Increase
Decrease
collagen fibers
active fibroblasts
capillaries
Gross Picture
Granulation tissue
pink soft
moist
bleeds in touch
insensitive
Resistant to bacterial infection.
Microscopic Picture
always present in granulation tissue.
capillaries
fibroblast odema
inflammatory cells
macrophages, lymphocytes,
eosinophils, mast celles neutrophils, Macrophages.
Def: the process of recovery in which the body replaces the damaged or lost tissues by new healthy tissues
Resolution, Regeneration & Organization

10. Healing
Resolution
complete restoration of normal conditions after acute inflammation
main features
Minimal cell death and tissue damage.
Rapid elimination of the causal agent
Local conditions favoring removal of fluid and debris.
Pathophysiology
Fibrinolysin Solution of fibrin by enzyme action
Removal of fluid by blood vessels and lymphatics.
Removal of debris by phagocytes to regional lymph nodes
hyperemia diminishes
restoration to normal is complete.
Ex: Resolution of lobar pneumonia bacterial inflammation of alveoli
Regeneration
the damaged tissue is replaced by a new one of the same type
depends on
type of the cell
power of proliferation.
Pathophysiology
2 main
components
Movement of surviving cells
into the vacant space made
available by loss of tissue due
to wounding or necrosis.
Proliferation of surviving
cells to replace the loss.
probable
mechanisms
Removal of
contact inhibition
allows movement of the cells
laterally to cover wound surface
cells in close contact inhibit cell migration
only move vertically to replace surface loss
Removal of
CHALONES
chemical factors inhibiting mitosis
in neighboring cells of the same type
by prolonging the G1 phase of the cell cycle
allows proliferation of the surviving cells
Release of growth
stimulating factors
Initiation
cell division in G1&G0
due to specific growth factors
Potentiation
stimulate divided cells to enter S phase of cell cycle
EGF
PDGF
due to(non-specific)growth
factors(potentiators)
insulin
hydrocortisone
growth hormone
Important factors
The availability of a good blood supply
The survival of the supporting framework
allowing the cells to grow in an organized way

11. Neoplasia
Def: an abnormality of control of growth, differentiation and maturation of cells
Recognized by the formation of amass of tissue (neoplasm or tumor)
Biologic behavior
Benign Neoplasm
Locally Malignant Neoplasm
Malignant Neoplasm
neither invade nor spread
Locally invasive only
without distant spread
Invade & spread
LABORATORY
DIAGNOSIS
OF CANCER
Histologic examination
the most important method of diagnosis
aided by clinical data.
Fine-needle
aspiration (FNA)
aspiration of cells and fluids from tumors
present in Palpable sites
breast
thyroid
lymph nodes
Ultrasonic guided aspiration in deep seated tumors
Cytologic smears
tumours of bronchi and stomach
diagnose
dysplasia
carcinoma in situ
invasive carcinoma of uterine cervix
Immuno-histochemistry
detection of
cell products
surface markers
by using antibodies
Tumor markers
tumor associated molecules that can be detected in blood
alpha-fetoprotein inhepatocellular carcinoma
prostatic specific antigen in prostatic carcinoma.
Chromosomal analysis
diagnosis of lymphoid tumours
arrangement of genes
DNA ploidy analysis
measurement the DNA cells
to know
diploid (normal DNA)
aneuploid (abnormal DNA).

12. Carcinogenesis=Etiology of tumors
Genetic
Growth
promoting genes
(proto-oncogenes)
Genes
suppressor genes
(anti-oncogenes).
Genes that
regulate apoptosis
(cell death)
may be
converted to
oncogenes by
Point mutation
permanent
changes
in DNA
Chromosomal
translocation
Rearrangement
of genetic material
Burkitt s
lymphoma
Chromosomal
deletion
Deletion of
one arm of
a chromosome
Gene
amplification
Reduplication of DNA
production
hundreds copies
protoIt oncogene
breast cancer
proto-oncogenes
normal cellular genes
affect growth and Differentiation
Oncogenes
genes whose products are associated
with neoplastic transformation

13. Environmental causes
Factors which may activate cellular oncogenes
Chemical agents
Polycyclic hydrocarbons
Azo and amino compounds
(aniline dye and rubber industries)
carcinoma of
liver
urinary bladder
skin and bronchognic carcinoma.
Asbestos malignant mesothelioma
Viruses
Human Papilloma Virus (HPV)
benign squamous cell papilloma
carcinoma of the cervix.
Epstein-Barr Virus (EBV)
member of herpes family
nasopharyngeal carcinoma
Burkitt's lymphoma
Hepatitis B and C viruses (HBV and HCV) hepatocellular carcinoma.
Human T cell leukaemia virus (HTLV)
leukaemia
lymphoma
Radiation
Ultraviolet rays
derived from sun
skin cancer
malignant melanoma
Ionizing irradiation myeloid leukaemia
carcinoma of skin.
thyroid cancer in children
Hormones
no evidence that hormones by themselves cause cancer
the rate of growth of breast and endometrial cancer is dependent upon oestrogen
prostate cancer is stimulated by testosterone
prostate cancer is depressed by oestrogen.
Heredity
retinoblastoma
breast cancer
familial adenomatous polyposis
diet and alcohol

15. HT
Hypertension
high blood pressure
Blood pressure
measurement of the force against the
walls of your arteries as the heart pumps blood
measured in millimeters of mercury (mmHg)
usually given 120 over 80 (120/80mm Hg)
One or both of these numbers can be too high
The top number
systolic pressure
high over 140 most of the time.
normal below 120 most of the time
The bottom number
diastolic pressure.
high over 90 most of the time.
normal below 80 most of the time
Pre-hypertension
Top number between120&139 most of the time
Bottom number between80&89 most of the time
most likely one to have hypertension
= Cardiac output×Peripheral resistance
increases the total peripheral resistance and the cardiac out
Cardiac output(C.O) = H.R (heart rate) ×S.V(stroke volume).
Primary=essential without apparent cause
Secondary with known cause
Risk Factors
Increase with age Obesity Family history
Tobacco use High intake of alcohol Stress
High intake of sodium Sedentary life style

16. Pathogenesis
2-High vasomotor tone causing increases vascular resistance.
1-Thickening of the arteriolar wall which might be genetic in origin.
3-Increased blood flow resulting from
renal (rennin)
hormonal dysfunction
aldosterone hormone
corticosteroid hormone
4-Renin-
angiotensin
mechanism
Decrease in renal blood flow
Secretion of rennin
The liver secretes angiotensinogen
conversion of Angiotensinogen by the action of renin into angiotensin I
Conversion of Angiotensin I into Angiotensin II by the action of angiotensin
converting enzyme (ACE)
secretion of(ACE) from the surface of pulmonary and renal epithelium.
Angiotensin
II causes
Aldosterone secretion from the adrenal gland cortex
Sympathetic activity
Arteliolar vasoconstriction
increase in blood pressure
(passive transport)
An inhibitory signal is sent to the kidney
to decrease the secretion of rennin
Angiotensin&aldosterone
Na+ Cl reabsorption
K excretion
H2O retention.
antidiuretic hormone
H2O and salt retention
increase in blood volume
Perfusion of the juxtaglomerular
apparatus(blood flow) increases
Hypertention Theories:-

17. HT Complications
Angina and
myocardial infarction
Hypertension will reduce the blood flow to the myocardium
Left ventricular failure
increased aortic vascular resistance
backpressure
Cerbro-vascular accident
cerebral hemorrhage
subarachnoid hemorrhage
Dissecting aortic aneurysm
layers of aortic wall are splitted
blood passes through it
severe pain
bad prognosis
HT crisis
a severe increase in arterial blood pressure
result in
Pathophysiology
renal, cardiac or cerebral complication
death
Causes
Same as complications
Impaired renal function
Hypertensive encephalopathy
Myocardial ischemia=hypoxia=cerebral infraction
Eclampsia
Pheochromocytoma (suprarenal medulla tumor)
End organ failure

18. HF
A state in which the heart cannot provide sufficient cardiac output to satisfy the needs of the body.
The heart muscle cannot pump(eject) the blood out of the heart very well
The heart muscles do not fill up with blood easily AS it become stiff
the heart is no longer able to pump enough oxygen&nutrients-rich blood out to the rest of your body
blood may back up other areas of the body
symptoms and effects may differ from patient to patient
Heart muscle has difficulty contracting.
the heart's ability to contract decreases.
causes pulmonary congestion(fluid in lung)
Heart muscle has difficulty relaxing
lead to fluid accumulation,in the feet,ankles,&legs and lung congestion.
reduces organs ability to work
two categories
causes
effects
characters
of patient
right –sided
Congestive
(diastolic)HF
Left –sided
Congestive
(systolic)HF
in health the function of both ventricles is closely integrated
both ventricles have the same capacity, pump virtually synchronously.
the action of each ventricle is not isolated
both influences and is influenced by the action of the other
combined failure are common
one side of the heart usually fails first, followed by other side.
It is helpful in the early stages to refer as left- sided GHF or right –sided GHF

19. HF pathophysiology
HF is secondary to
systolic dysfunction
diastolic dysfunction
Hemodynamic
Changes
ex:
the blood pressure&blood flow
at the output of the left heart.
Cellular
changes
affects contraction of myocardium
Changes in
adrenergic
receptors
Changes in
Ca+2 ions handling
found in the myocardium
Slight increase in α1 receptors.
β1 receptors desensitization to catecholamine
Changes in contractile proteins in the muscle fibers
Program cell death (Apoptosis).
Increase amount of fibrous tissue
β1 Receptors and α1 receptors (↑contractility).
NB:
Neuro
hormonal
changes
decrease tissue perfusion(blood flow)
decreasing renal perfusion salt and water retention
increased blood pressure
increased sympathetic output increases renin release
high sympathetic &
rennin angiotensin
activity
compensate for heart failure
by increasing cardiac output
through increasing
peripheral resistance
myocardial contractility
heart rate
eventually triggers
myocyte hypertrophy
apoptosis
focal necrosis
Circulating
endothelin-1
(ET-1)
present in high levels during heart failure
causes
vasoconstriction
hyperplasia
fibrosis