Disorders of blood circulation and of lymph.

Cellular adaptations II. Healing.

(Brown induration of lungs, chronic venostasis of liver, pulmonary artery embolism,

lung edema, hypertrophy of myocardium, metaplasia, organisation of

fibrinous perotonitis, organisation of thrombus, healing of MI,

foreign body granuloma)

General Medicine

Svetoslav Štvrtina, M.D., PhD.

Michal Palkovič, M.D., Ph.D.

Vladimír Šišovský, M.D., Ph.D. František Kiš

Department of Pathology, FMCU and FH Work place Staré mesto

Sasinkova 4, Bratislava

Prof. MUDr. Ľudovít Danihel, CSc.

Disorders of blood

circulation (B.C.)

• Systemic

• Local

Disorders can be:

+

-

Different division:

(+) Disorders

• Hyperemia

• Increased volume of blood

• Increased number of blood elements

• Increased volume of fluids and

electrolytes

• Increased permeability of capillaries

• Increased coagulability of blood

• Increased blood pressure

(-) Disorders

• Heart failure

• Decreased blood pressure

• Disorders of the amount and

composition of blood

• Disorders of circulatory system

integrity

Disorders of blood circulation

To maintain normal blood flow:

1.Normal anatomic features

2.Normal physiologic controls for blood flow

3.Normal biochemical composition of the blood

Haemodynamic disturbances:

1.Disturbances in the volume of the circulating blood

(hyperaemia, congestion, haemorrhage, shock)

2.Circulatory disturbances of obstructive nature

(thrombosis, embolism, ischaemia, infarction)

Disturbances in the volume of circulating blood

Hyperaemia (active hyperaemia) – increased

volume of blood from arterial and arteriolar

dilatation (e.g. inflammation, high grade fever)

- clinically - redness, raised temperature

Venous congestion (passive hyperaemia,

venostasis) – dilatation of veins and capillaries due to

impaired venous drainage

- clinically – bluish colour (cyanosis)

- acute / chronic

1. local – e.g. portal venous obstruction in cirrhosis of the

liver

2. systemic (general) – in left-sided heart failure

(pulmonary congestion), in right-sided heart failure

(chronic venous congestion of the liver, spleen, kidney)

• Left heart failure

• Blood stasis in lungs with dilatated capillaries filled with Er

• Accumulation of fluid in alveoli

• Acculmulation of erythrocytes in alveoli → Phagocytosis of erythrocytes → Metabolic change of hemoglobin to hemosiderin → Creation of siderophages („heart failure cells“)

• Fibrosis of alveolar septi

• Pulmonary hypertension

Brown induration of lungs (157)

• right heart failure, occlusion of inferior vena cava, hepatic vein

• yellowbrown liver tissue with dark red foci – nutmeg liver, later opposite image

• dilatation of central veins and sinusoids → pressure atrophy or hypoxic necrosis of centrolobular hepatocytes and hypoxic steatosis of peripheral hepatocytes

• later - accumulation of

connective tissue – fibrosis

(cardiac)

Chronic venostasis of liver (10)

Chronic venostasis of liver.

Disturbances in the volume of

circulating blood

• Collapse (orthostatic collapse) - sudden transient circulation failure

• Shock – profound failure of circulation to

maintain appropriate blood supply of vital organs

– cardiogenic

– hypovolemic

– septic (toxaemic)

– others (traumatic, neurogenic,...)

Shock kidneys (327) Macro : large, swollen kidney, congested, but the cortex

may be pale. A cross-section shows blood pooling in the

outer stripe od medulla.

Micro : acute tubular necrosis – dilatation of the proximal

tubules, focal cell necrosis, pigmented casts in the tubular

lumina, interstitial edema.

Shock adrenal gland (328)

Macro : conspicuous hemorrhage in the inner cortex.

(Waterhouse-Friderichsen syndróm)

Micro : necrosis, intracapillary haemocoagulation,

increase in ACTH secretion, widening of the space

between trabeculae (oedema) and thinning of the

trabeculae - pseudotubular degeneration

Circulatory disturbances of

obstructive nature

• trombosis

• embolism

• ischaemia

• Infarction

Ischemia

– deficient blood supply (obstruction,

compression, spasm,...)

– ischemia ... Infarction (necrosis)

Trombus, trombosis

Thrombus (aggregate of coagulated blood within vascular lumen,

adheres to EC)

- in the heart, arteries, veins, microcirculation

- Virchow trias – 1. endothelial injury

2. altered blood flow

3. hypercoagulability

Grossly:

– white thrombus (arterial)

– red thrombus (venous)

– mixed thrombus

- lysis / propagation / organisation / recanalisation

Arterial thrombi - ischaemia...necrosis

Cardiac, venous thrombi - tromboembolism

Microthrombi in microcirculation - DIC

Embolus (material carried in the bloodstream that can lead

to vessel obstruction)

a) solid (trombus, tumour cells, parasites,

bacterial clumps, foreign bodies)

b) liquid (amniotic fluid, fat, bone marrow)

c) gaseous (air)

- paradoxical embolus

- retrograde embolus

Embolus, Embolism

• Most often by blood thrombus (from deep

veins of lower extremities)

• Other possibilities: malignant cells, air, fat,

amniotic fluid, bacteria

• Results depends on size of the embolus:

- asymptomatic / minor dyspnoea →

pulmonary hypertension and RV failure

- pulmonary infarction

- cardiovascular collapse with sudden death

Pulmonary artery embolism (7)

Embolus

Lungs

Embolus

Thrombus (embolus) Lungs – venostasis and bleedig

1.Oedema

2.Dehydratation

3.Overhydratation

Disturbances of body fluids

- excess of fluid in interstitial spaces, cavities

- localised (inflammation, allergy, venous or lymphatic

obstruction)

- generalized (heart failure, renal, hepatal disease...)

• Causes

– Increase of hydrostatic pressure (art,.,venous)

– Decreased content of proteins in serum (oncotic)

– Increased permeability of capillaries

– Disorder of lymphatic drainage

– Sodium and water retention

Oedema

Arteriole Venule

Lymphatic vessel with node

Capillary

AP VP B B 4,27 kPa 1,6 kPa

3,33 kPa 3,33 kPa

Arteriole Venule

Lymphatic vessel with node

Capillary

AP VP B B

Norm (standard)

10% 100% 90%

Arteriole Venule

Lymphatic vessel with node

Capillary

AP VP B B

Venostasis

30%

X X X

X X X

Arteriole Venule

Lymphatic vessel with node

Capillary

AP VP B B

Proteins

X X X

X X X

Arteriole Venule

Lymphatic vessel with node

Capillary

AP VP B B

Inflammation

X X X

X X X

Arteriole Venule

Lymphatic vessel with node

Capillary

AP VP B B

Lymphostatic

edema

X

X

X X X

X X X

• Accumulation of liquid first in the interstitium and

later in alveoli

• Causes – left heart failure, inflammation,

disorders of blood plasma composition,

disorders of lymphatic drainage, combination

• Histology: light pink homogenous material in

alveoli – by fixation coagulated proteins of

edematous liquid

• Optically empty rounded spaces – air bubbles

Lung oedema (265)

Disorders of lymphatic drainage -

lymphoedema

• removal of axillary lymph nodes (in radical

mastectomy)

• pressure from outside (tumours)

• injury of thoracic duct

• chylothorax

• chylous ascites

• inflammation of the lymphatics (filariasis –

elephantiasis)

• occlusion of lymphatic channels by

malignant cells

• Milroy's disease -hereditary lymphoedema

Cellular adaptations

• Physiologic adaptation – to the physiologic needs

• Pathologic adaptation – to non-lethal pathologic injury

• Adaptations:

• 1. atrophy – reduction of the number and size of cells

• 2. hypertrophy – increase in size of cells

• 3. hyperplasia – increase in number of cells

• 4. metaplasia – reversible change of one type of mature cells to another type of mature cells

• 5. dysplasia – disordered cellular development

Hypertrophy

• enlargement of cell volume

Hypertrophy

• Physiologic (enlarged size of the uterus in

pregnancy, also hyperplasia)

• Pathologic:

1.hypertrophy of cardiac muscle

2.hypertrophy of smooth muscle

3.hypertrophy of skeletal muscle

4.compensatory hypertrophy

• Hypertension in PC

- acute – RV dilatation (cor pulmonale acutum)

- chronic – RV hypertrophy (cor pulm.chron.)

• Hypertension in SC

• esencial / secundary hypertension

• LV hypertrophy (cor hypertensivum)

→ cor bovinum

• Hypertrophy

– concentric – pressure overload

– eccentric – volume overload

Myocardial hypertrophy

Hypertrophy of myocardium (291)

Hyperplasia

• increas of cell number

Hyperplasia

• Physiologic:

1.hormonal (pregnant uterus, female breast during

lactation)

2.compensatory (liver after partial hepatectomy)

• Pathologic:

• endometrial hyperplasia in oestrogen excess

• intraductal epithelial hyperplasia in the breast

• skin wart from hyperplasia of epidermis (HPV)

Metaplasia

– change of one differenciated tissue to another

Metaplasia

• Epithelial:

1.squamous (bronchus, uterine cervix)

2.columnar (intestinal metaplasia in gaster, Barrett's

oesophagus)

• Mesenchymal:

1.osseous (in scar, fibrous stroma of tumour)

2.cartilaginous (in wrong healing fractures)

Metaplasia (174)

Dysplasia

= atypical hyperplasia

•most often in epithelial cells (uterine cervix,

respiratory tract) – cellular proliferation and

cytologic changes

•may progress into carcinoma in situ,

invasive cancer

Healing

• Body response to injury – to restore

normal structure and function

• Regeneration – Replacement of damaged tissue by equivalent

tissue, proliferation of parenchymal cells

• Repair – Replacement of damaged tissue by second

rate tissue, proliferation of connective tissue

elements→fibrosis, scarring

- mostly combination of both

Regeneration

– replacement of damaged tissue by equivalent tissue

Regeneration

• According to regeneration capacity

the cells are classified:

– Unstable – regularly replaced : hematopoiesis, epithelia, axon

– Stable – renewed is only damaged

tissue: glandular epithelium, proximal canaliculi,

vascular smooth muscle

– Permanent – ganglion cells, crosstriated muscle

Repair

– replacement of damaged tissue by second rate tissue (fibrous)

Repair

1. Granulation tissue formation

2. Contraction of wounds

• Wound healing

– primary (per primam intentionem)

– secondary (per secundam intentionem)

• Organisation of hematoma and

thrombus

• Healing of bone fracture

• Healing of foreign bodies

• Organisation of fibrinous exudates

Wound healing

• Combination of regeneration and repair

Healing of fractured bone

Healing of fractured bone

hematoma

Healing of fractured bone

Fibrous callus

Healing of fractured bone

Osseous (bony) callus

Healing of fractured bone

Definitive callus

Fibrinous peritonitis in organisation(163)

Thrombus in organisation

• Thrombus is resorbed and replaced

by connective tissue

• Granulation tissue grows into the

thrombus

• Granulation tissue eliminates

thrombus and ingrowing capillaries

open their lumen - recanalisation

Organisation of thrombus

Organisation of thrombus

Organisation of thrombus

Organisation of thrombus

Organisation of thrombus

Organisation of thrombus

Mixed thrombus

Ingrowing capillaries

Healing of myocardial infarction

(293)

• granulation tissue formation

• scar maturation

Incorporation of foreign body

• Foreign body (of endogenous or

exogenous origin) – it cannot be

removed by common means such as:

– dissolving

– diluting

– phagocytosis

– elimination

Incorporation of foreign body

• Creation of granuloma around the

foreign body:

– large multinucleated cells around foreign

bodies

– connective tissue

– lymphocytes

– histiocytes

• Sometimes the granuloma grows too

large

– Schloffer’s tumor

• Scar after cholecystectomy

• Surgical stiches in 2nd picture

• Circumscribed by connective tissue

• Large cells around foreign bodies try to

phagocyte the fibres

Foreign body granuloma (19)

Large cells around

foreign bodies