PATHOLOGY:

L AB REVIEWER
MD2021
1ST SEM, PRELIMS
CHAPTER 2:
CELLUL AR
RESPONSES
CELLULAR ADAPTATIONS
 1. HYPERTROPHY

• Increased cell size

• Due to the synthesis of and assembly of additional intracellular structural components
• Mechanism: Inc. production of cellular proteins
• Non-dividing cells
• Can be physiologic or pathologic
• Physiologic:
– Inc. functional demand (skeletal muscles, cardiac muscles)
– By stimulation of hormones & growth factors (uterus)
• Most common stimulus for muscle hypertrophy: increased workload
 1. HYPERTROPHY

• GRAVID UTERUS (UTERINE HYPERTROPHY)

• Physiologic hypertrophy of myometrium
• due to stimulation of hormones (estrogen) -> inc.
synthesis of smooth muscle proteins -> inc. cell size
1. HYPERTROPHY

• CARDIAC HYPERTROPHY
• Diagnosis: Cardiomegaly
• Stimulus: chronic hemodynamic overload due to:
– Hypertension
– Faulty valves
 2. HYPERPLASIA
• Increase in the number of cells
• Cells capable of dividing
• Mechanism: growth-factor driven proliferation of mature cells and inc. output of new cells from tissue stem cells
• 1. PHYSIOLOGIC:
– Due to action of hormones or growth factors
– When there is a need to:
• Inc. functional capacity of hormone sensitive organs (HORMONAL HYPERPLASIA)
– Proliferation of the glandular epi. of female breast at puberty and during pregnancy
• For compensatory inc. after damage or resection (COMPENSATORY HYPERPLASIA)
– Liver regeneration: individuals who donate one lobe of liver for transplantation, the remaining cells proliferate so that the organ soon grows back
to its original size
– Bone marrow: in response to deficiency of terminally differentiated blood cells (acute bleed/ hemolysis)

• II. PATHOLOGIC:
– Fertile soil for malignancy
– Due to excessive or inappropriate actions of hormones or GF
• Endometrium - estrogen
• benign prostatic hyperplasia- androgens
– In response to viral infections (HPV-skin warts)
2. HYPERPLASIA
• THYROID HYPERPLASIA (Grave’s Disease)
• Due to TSH/ TRH stimulation
• S/S:
– Bulging eyes (exophthalmos)
– Anxiety and irritability
– A fine tremor of your hands or fingers
– Heat sensitivity and an increase in perspiration or warm, moist skin
– Weight loss, despite normal eating habits
– Enlargement of your thyroid gland (goiter)
– Change in menstrual cycles
– Erectile dysfunction or reduced libido
– Frequent bowel movements
– Bulging eyes (Graves' ophthalmopathy)
– Fatigue
– Thick, red skin usually on the shins or tops of the feet (Graves' dermopathy)
– Rapid or irregular heartbeat (palpitations)
2. HYPERPLASIA

• ENDOMETRIAL HYPERPLASIA
• pathologic
• Pinkish: myometrium ; brown: endometrium
• Prolonged Inc. estrogen; dec. progesterone
• Common cause of abnormal menstrual
bleeding
• Elongated cigar-shaped nuclei
• “gland crowding”
 3. ATROPHY

• Decrease in cell size and number

• Mechanism: dec. protein synthesis (reduced metabolic activity) and inc. protein degradation
• I. PHYSIOLOGIC
– Common during normal development
– Notochord and thyroglossal duct during fetal development
– Dec. in size of uterus after parturition
• II. PATHOLOGIC
– Dec. workload
– Loss of innervation
– Diminished blood supply
– Inadequate nutrition
– Loss of endocrine stimulation
– Pressure
 BRAIN TESTICULAR
ATROPHY ATROPHY

• Dure to dec. in hormones

4. METAPLASIA
• Reversible change in which one differentiated cell type is
replaced by another cell type
• Mechanism: does not result from a change of an already
differentiated cell type; instead it is a result of reprogramming
of stem cells that are known to exist in normal tissues, or
undifferentiated mesenchymal cells

• SQUAMOUS METAPLASIA
– Columnar to squamous
– Ciliated columnar epi. cells of the trachea and bronchi are
replaced by stratified squamous epi cells
– Chronic irritation from cigarette smoke
 4. METAPLASIA

• BARRETT ESOPHAGUS
- Squamous to columnar
- Esophageal squamous epi. is replaced by intestinal-like
columnar cells due due to refluxed gastric acid
- Give rise to adenocarcinomas (glandular)
 CELLULAR INJURY & CELL DEATH
• REVERSIBLE CELL INJURY
– Hallmarks:
• Reduced oxidative phosphorylation -> low
ATP
• Cellular swelling
– Can be recognized under the microscope as:
• Cellular swelling
• Fatty change

• IRREVERSIBLE INJURY • CAUSES OF CELL INJURY:

– Leads to cell death: – Oxygen deprivation
• Necrosis – Physical agents
• Apoptosis – Chemical agents and drugs
– Infectious agents
– Immunologic reactions
– Genetic derangements
– Nutritional imbalances
REVERSIBLE INJURY IRREVERSIBLE INJURY
 NECROSIS
• Result of denaturation of intracellular proteins and enzymatic digestion of injured cell

• PYKNOSIS- chromatin condensation

• KARYORRHEXIS – nuclear fragmentation
• KARYOLYSIS – complete dissolution of chromatin
PATTERNS OF TISSUE NECROSIS: COAGULATIVE

ACUTE
TUBULAR
NECROSIS
PATTERNS OF TISSUE NECROSIS: LIQUEFACTIVE

BRONCHOPNEUMONIA
ACUTE SUPPURATIVE APPENDICITIS
• Liquefactive necrosis
PATTERNS OF TISSUE NECROSIS: GANGRENOUS
PATTERNS OF TISSUE NECROSIS: CASEOUS
PATTERNS OF TISSUE NECROSIS: FAT NECROSIS

ENZYMATIC FAT NECROSIS

PATTERNS OF TISSUE NECROSIS: FIBRINOID
 APOPTOSIS

• Induced by regulated suicide program in which cells destined to die

activate intrinsic enzymes that degrade the cells’ own nuclear DNA
and nuclear and cytoplasmic proteins
• Results from activation of enzymes called caspases
• 2 pathways:
• Intrinsic (Mitochondrial)
• Extrinsic (Death receptor-initiated)
 APOPTOSIS
P H YSI O LO G I C PAT H O LO G I C

• Destruction of cells during embryogenesis • DNA damage

• Involution of hormone-dependent tissues upon • Accumulation of misfolded proteins
hormone withdrawal
• Cell death in certain infections
• Cell loss in proliferating cell populations
• Pathologic atrophy in parenchymal organs
• Elimination of potentially harmful self-reactive
after duct obstruction
lymphocytes
• Death of host cells that have served their
useful purpose
 INTRACELLULAR ACCUMULATIONS
• 4 main pathways:
– Abnormal metabolism
– Defect in protein folding, transport
– Lack of enzyme
– Ingestion of indigestible materials

• Lipids
• Proteins
• Hylaline change
• Glycogen
• Pigments
STEATOSIS (FATTY CHANGE)
• FATTY LIVER
• Abnormal accumulations of
triglycerides within
parenchymal cells
• Causes:
• Alcohol abuse
• Nonalcoholic abuse (diabetes
& obesity)
• Toxins
• Protein malnutrition
• DM
• anoxia
CHOLESTEROLOSIS

• Focal accumulations of cholesterol

laden macrophages in the lamina
propria of the gallbladder
• Cholesterol = synthesis if cell
membranes
• Seen in:
• Antherosclerosis
• Xanthomas
• Cholesterolosis
• Niemann-Pick disease, type C
PROTEINS
 ANTHRACOSIS

• ANTHRACOSIS (lungs)
• Most common exogenous pigment is carbon (coal dust)
 LIPOFUSCIN

• an insoluble pigment aka lipochrome or wear-and-tear pigment

• Not injurious; telltale sign of free radical injury and lipid peroxidation
• Yellow-brown finely granular cytoplasmic, often perinuclear, pigment
• Prominent in heart and liver of aging patients or those with severe malnutrition and cancer cachezia
• Other endogenous pigments:
– MELANIN: only endogenous brown-black pigment
– HEMOSIDERIN: hemoglobin-derived, golden-yellow-to-brown, granular or crystalline pigment; one of the
major storage forms of iron
INTRADERMAL NEVUS
• an endogenous, brown-black, pigment
• formed when the enzyme tyrosinase catalyzes
the oxidation of tyrosine to
dihydroxyphenylalanine in melanocytes.
• the only endogenous brownblack pigment.
• The only other that could be considered in this
category is homogentisic acid, a black pigment
that occurs in patients with alkaptonuria, a rare
metabolic disease.
• Here the pigment is deposited in the skin,
connective tissue, and cartilage, and the
pigmentation is known as ochronosis.
CHAPTER 3:
I N F L A M M AT I O N
AND
R E PA I R
MONCKEBERG CALCIFICATIONS
• DYSTROPHIC CALCIFICATION

– Necrotic or dying tissues

– Normal calcium levels
– Telltale sign of previous injury (calcific
valvular dse, atherosclerosis)

• METASTATIC CALCIFICATION
– Normal tissue
– Hypercalcemia
– Causes of hypercalcemia:
• Inc secretion of PTH
• Resorption of bone tissue
• Vit D related disroders
• Renal failure
 ACUTE INFLAMMATION

Acute inflammation has three major components:

• Causes of inflammation:
(1) dilation of small vessels leading to an increase in blood flow
– Infections
(2) increased permeability of the microvasculature – Tissue necrosis
enabling plasma proteins and leukocytes to leave the circulation
– Foreign body
(3) emigration of the leukocytes from the microcirculation, their
– Immune reaction
accumulation in the focus of
injury, and their activation to eliminate the offending
agent
 SEROUS INFLAMMATION:
SKIN BLISTER

• Serous inflammation is marked by the exudation of cell-poor fluid

 FIBRINOUS INFLAMMATION:
FIBRINOUS PERICARDITIS

• A fibrinous exudate develops when the vascular leaks are large or there is a local procoagulant
stimulus
PURULENT/SUPPURATIVE INFLAMMATION:
ACUTE APPENDICITIS

• Purulent inflammation is characterized by the

production of pus, an exudate consisting of
neutrophils, the liquefied debris of necrotic cells, and
edema fluid.
PURULENT/SUPPURATIVE INFLAMMATION:
BRONCHOPNEUMONIA
 ULCER

• An ulcer is a local defect, or excavation, of the surface of an organ or tissue that is produced by the
sloughing (shedding) of inflamed necrotic tissue
CHRONIC INFLAMMATION
• Chronic inflammation is a response of prolonged duration
(weeks or months) in which inflammation, tissue injury and
attempts at repair coexist, in varying combinations.
• Causes:
– Persistent infections
– Hypersensitivity diseases
– Prolonged exposure to potentially toxic agents
• Morphologic features:
– Inflitration with mononuclear cells
– Tissue destruction
– Attempts at healing
GRANULOMATOUS INFLAMMATION
• Granulomatous inflammation
is a form of chronic
inflammation characterized by
collections of activated
macrophages, often with T
lymphocytes, and sometimes
associated with central
necrosis.
• Granuloma formation is a
cellular attempt to contain an
offending agent that is difficult
to eradicate.
CHRONIC CHOLECYSTITIS
 TISSUE REPAIR
• REGENERATION
– Labile tissue: continuously dividing (hematopoietic cells,
surface epithelia)
– Stable tissue: quiescents (G0 stage); capable of dividing in
response to injury; liver, kidney, pancreas, endothelial cells,
fibroblasts, smooth muscle; limited capacity to regenerate
except liver
– Permanent tissue: terminally differentiated and
nonproliferative in postnatal life; neurons and cardiac
muscles
• CONNECTIVE TISSUE DEPOSITION (SCAR
FORMATION)
– Angiogenesis (VEGF)
– Formation of granulation tissue
• Migration and proliferation of fibroblasts and deposition
of loose connective tissue, blood vessels, and leukocytes
– Remodeling of connective tissuec
• Factors that influence tissue repair:
– Infection, Diabetes, Nutritional status, Glucocorticoids, Mechanical
factors, Poor perfusion, Foreign bodies, Type and extent of tissue
injury, Location of the injury
• Healing of skin wounds:
– By 1st intention:
• Day 1: neutrophils at incision margin migrating toward fibrin clot; inc.
mitotic activity of basal cells
• Day 3: neutrophils replaced by macrophages and granulation tissues
invade incision space; collagen fibers are evident; epithelial cell
proliferation
• Day 5: neovascularization, granulation tissue fills incisional space;
migration of fibroblasts (ECM proteins and collagen fibrils)
• 2 weeks: inc collagen deposition, regression of vascular channels
• 1 month: connective tissue devoid of inflammatory cells, normal
epidermis
– By 2nd intention:
• More extensive (large wounds, abscesses, ulceration, ischemic necrosis
in parenchymal organs
• Combination of regeneration and scarring
GRANULATION TISSUE
 • INADEQUATE FORMULATION OF GRANULATION TISSUE

ULCER DEHISCENCE

• Inadequate vascularization during healing

• rupture of wound due to mechanical stress (inc.
pressure)
• EXCESSIVE FORMATION OF COMPONENTS OF REPAIR PROCESS

HYPERTROPHIC SCAR

• Accumulation of excessive collagen

• Raised scar
• Does not go beyond the border of original wound
 • EXCESSIVE FORMATION OF COMPONENTS OF REPAIR PROCESS

KELOID

• Accumulation of excessive collagen; Raised scar

• Scar tissue goes beyond the boundaries of original wound and does not regress
 EXUBERANT GRANULATION

• Excessive amounts of granulation tissue which protrudes above the level of the
surrounding skin and blocks reepithelialization
• Increased collagen, fibroblasts, blood vessels
CONTRACTION

• Serious burns
• Can compromise movement of joints
CHAPTER 4:
HEMODYNAMIC
DISORDERS
PULMONARY EDEMA

• Left-sided heart failure, renal failure, ARDS

LARYNX EDEMA

• Causes of edema:
– Inc hydrostatic pressure (blood volume)
– Dec plasma osmotic pressure (albumin)
– Sodium and water retention
– Lymphatic obstruction
 LIVER WITH CHRONIC PASSIVE CONGESTION

• As a result of increased hydrostatic pressures, congestion commonly leads to edema.

• In long-standing chronic passive congestion, the associated chronic hypoxia may result in ischemic tissue
injury and scarring.
• In chronically congested tissues, capillary rupture can also produce small hemorrhagic foci;
subsequent catabolism of extravasated red cells can leave residual telltale clusters of hemosiderin-
laden macrophages.
 HEMORRHAGIC DISORDERS

• Caused by:
– Defects of primary hemostasis (platelet defects or von willebrand disease)
– Defects of secondary hemostasis (coagulation factor defects)
– Generalized defects involving small vessels (palpable purpura, ecchymoses)
HEMORRHOIDS
HEMORRHOIDS WITH THROMBI
HEMOTHORAX
 MURAL THROMBI

• THROMBUS • FATE OF THROMBUS • MURAL THROMBI

– Endothelial injury – Propagation – Heart chambers or aortic
– Alterations in blood flow: turbulence – Embolization lumen
or stasis – Abnormal myocardial
– dissolution
– Hypercoagulability contraction
– Endomyocardial injury
 THROMBI
V E N O U S TH RO M BI A RT E R I A L T H RO M B I

• Painful congestion and edema • Major cause: atherosclerosis

• Embolize to the lungs • MI – cardiac mural thrombi
• 1. Superficial venous thrombi • Rheumatic heart dse – atrial mural thrombi
– Saphenous vein in the setting of
• Prone to embolization
varicosities
– Local congestion, swelling, pain, rarely
embolize
• II. Deep venous thrombi
– Embolize to the lungs
– asymptomatic
 PULMONARY EMBOLISM

• Main pulmonary artery

• Straddle the pulmonary artery bifurcation(saddle embolus)
• Pass out into sammaler branching arteries
BONE MARROW EMBOLISM
AMNIOTIC FLUID EMBOLISM
 INFARCT
• Ischemic necrosis caused by occlusion of
either arterial supply or venous drainage
• RED INFARCT:
– Venous scclusion
– Loose, spongy tissue
– Dual blood circulation
– Lungs, small intestine
• WHITE INFARCT:
– Arterial occlusion
– Solid organs
– End-arterial circulation
– Heart, spleen, kidney
SHOCK
CHAPTER 5:
GENETIC
DISORDERS
TAY SACHS DISEASE
• Inability to catabolize GM2
gangliosides
• Mutations in α- subunit of
chromosome 15
• Sever deficiency of
hexosaminidase A
• Normal at birth
• 6 months: motor and mental
deterioration (motor incoordination,
mental obtundation, muscular
flaccidity, blindness, increasing
dementia, cherry red spot
• 1-2 years: complete vegetative state
• 2-3 years: death
• Common among Jews
• B-subunit defect: Sandhoff disease
NIEMANN-PICK DISEASE
• Lysosomal accumulation of sphingomyelin
• Deficiency of sphingomyelinase (11p15.4)
• Maternal chromosome
• Autosomal recessive
• TYPE A:
– Severe infantile form
– Neurologic involvement
– Visceral accumulation of sphingomyelin
– Age 6: protruberant abdomen (hepatosplenomegaly), failure
to thrive, vomiting, fever, generalized lymphadenopathy,
deterioration of psychomotor function
– Progressive wasting and early death (3yrs)
• TYPE B:
– Organomegaly
– No CNS involvement
– survive into adulthood
– Common among Jews
• TYPE C:
– More common that type A and B
– Mutation in NPC1 (95%) NPC2 = transport of cholesterol
from lysosome to cytoplasm; defect in nonezymatic lipid
transport
– Hydrops fetalis, neonatal hepatitis
– More common: chronic form: progressive neurologic
damage, ataxia, vertical supranuclear gaze palsy, dystonia,
dysarthria, psychomotor regression
GAUCHER DISEASE
• Autosomal recessive
• Mutation in gene encoding glucocerebrosidase
• Glucocerebroside accumulation in phagocytes or CNS
• TYPE 1(most common)
– Chronic nonneuropathic
– Mononuclear phagocytes
– Splenic and skeletal
– Jews of European stock
– Reduced but detectable levels of glucocerebrosidase
activity
• TYPE 2
– Acute neuropathic
– Infantile acute cerebral pattern
– No predilection for Jews
– No detectable of glucocerebrosidase activity
– Hepatosplenomegaly, death at early age
• TYPE 3
– Intermediate of Type 1 and 2
– Systemic involvement and progressive CNS involvement
– Begins in adolescence or early adulthood
NEUROFIBROMATOSIS
GLYCOGEN STORAGE DISEASE: POMPE DISEASE
TRISOMY 21: DOWN SYNDROME
TRISOMY 18: EDWARD SYNDROME
TRISOMY 13: PATAU SYNDROME
KLINEFELTER SYNDROME
TURNER SYNDROME (XO)
TURNER SYNDROME (XO)

Turner syndrome (XO)