NEET MDS Lessons
General Pathology
Aneurysm
An aneurysm is a localized abnormal dilation of a blood vessel or the heart
Types:
1. True aneurysm - it involves all three layers of the arterial wall (intima, media, and adventitia) or the attenuated wall of the heart.
e.g. Atherosclerotic, syphilitic, and congenital aneurysms, and ventricular aneurysms that follow transmural myocardial infarctions.
2 False aneurysm
(also called pseudo-aneurysm) is a breach in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space ("pulsating hematoma").
E.g. ventricular ruptures after MI that are contained by a pericardial adhesion
E.g. a leak at the junction of a vascular graft with a natural artery.
Aneurysms are classified by macroscopic shape and size
Saccular aneurysms
spherical outpouchings (involving only a portion of the vessel wall, and often contain thrombi.
Fusiform aneurysms
diffuse, circumferential dilation of a long vascular segment;
they vary in diameter and length and can involve extensive portions of the aortic arch, abdominal aorta, or even the iliacs.
Aortic Aneurysm
The two most important causes are:
1- atherosclerosis : the most common cause
It causes thinning and weakening of the media. The intimal plaques compress the underlying media and also compromise nutrient and waste diffusion from the vascular lumen into the arterial wall. The media consequently undergoes degeneration and necrosis, thus allowing the dilation of the vessel
2- cystic medial degeneration of the arterial media. E.g. Marfan syndrome.
3- Other causes include: trauma, congenital defects (e.g., berry aneurysms), infections (mycotic aneurysms), systemic diseases, such as vasculitis.
Mycotic Aneurysm :
Infection of a major artery that weakens its wall is called a mycotic aneurysm
possible complications: thrombosis and rupture.
It can originate from:
(1) embolization of a septic thrombus, usually as a complication of infective endocarditis
(2) extension of an adjacent suppurative process;
(3) circulating organisms directly infecting the arterial wall
Mycotic AAAs are atherosclerotic lesions infected by lodging of circulating microorganisms in the wall
- e.g. bacteremia from a primary Salmonella gastroenteritis.
Abdominal Aortic Aneurysm
Atherosclerotic aneurysms occur most frequently in the abdominal aorta ,the common iliac arteries, the arch, and descending parts of the thoracic aorta can also be involved
Pathogenesis
AAA occurs more frequently in men and rarely develops before age 50.
Atherosclerosis is a major cause of AAA
hereditary defects in structural components of the aorta (e.g., defective fibrillin production in Marfan disease affects elastic tissue synthesis)
Morphology :
Usually positioned below the renal arteries and above the bifurcation of the aorta
AAA can be saccular or fusiform
as large as 15 cm in diameter, and as long as 25 cm.
Microscopically: atherosclerosis with destruction and thinning of the underlying aortic media
the aneurysm frequently contains a laminated mural thrombus
Syphilitic Aneurysm
Caused by The spirochetes T. pallidum
Tertiary stage of syphilis can cause obliterative endarteritis of the involve small vessels in any part of the body, including the vasa vasorum of the aorta
This results in ischemic medial injury, leading to aneurysmal dilation of the aorta and aortic annulus, and eventually valvular insufficiency.
valvular insufficiency and massive volume overload lead to hypertrophy of the left ventricle. The greatly enlarged hearts are sometimes called "cor bovinum" (cow's heart).
CLINICAL CONSEQUENCES
1. Rupture → massive potentially fatal hemorrhage
2. Obstruction of downstream vessel → tissue ischemic injury
3. Embolism → from atheroma or mural thrombus
4. Impingement and compression on an adjacent structure
5. Presentation as an abdominal mass
Acute leukaemia
Lympheblastic is commoner in children and myeloblastic in adults .
Features:
- Anaemia.
- Fever and infections especially oral and respiratory.
- Haemorrhagic tendencies.
- Bone pains and tenderness (sternal).
- Lymphnode enlargement especially in lymphocytic.
- Gum hypertrophy especially in monocytic.
Blood picture:
- Anaemia and thrombocytopenia.
- Leucocyte count usually 20,-50,000/cu.mm. It may be less in subleukaemic leukaemia (even leucopenic levels may be seen).
- Blast cells form 30-90% of cells. Smudge cells and basket cells are seen .The type of balst cell may be recognised by the associated more mature forms or by special cytochemical stains
- Blasts may be few in peripheral blood in the aleukamic stage
Bone Marrow
- May be a dry tap , necessitating a trephine biopsy
- Hypercellular with 70-90% blasts
- Reduction in megakaryocytes and erythroid cells
Streptococcal pharyngitis:
A disease of young people, enlarged lymphoid nodules and keratin plugs in the tonsillar pits is seen Complications include retro-pharyngeal abscess (quinsy)
Cellulitis of the deep tissues of the neck is Ludwig's angina
Scarlet fever ("scarlatina") is a strep throat caused by a streptococcus with the gene to make one of the erythrogenic toxins, Patients have a rash with PMNs
Streptococcal skin infections (Impetigo)
Erysipelas is a severe skin infection caused by group A strep; geographic of red, thickened, indurated areas of the skin are characteristic. Unlike staph infections, there is usually little or no tissue necrosis
Post-streptococcal hypersensitivity diseases include rheumatic fever, post-streptococcal glomerulonephritis, and some cases of erythema nodosum
Tuberculosis
Causative organism
-Mycobacterium tuberculosis
-Strict aerobe
-Pathogenic strains
-hominis, bovis, avium, murine& cold blooded vertebrate strain
Koch’s bacillus
-small slender, rod like bacillus, 4umnon-motile, aerobic -high lipid content
-divides every 16 to 20 hours, an extremely slow rate
-stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolicacid content of its cell wall
-can withstand weak disinfectant and survive in a dry state for weeks.
Demonstrated by
-ZiehlNeelsenstaining
-Fluorescent dye method
-Culture in LJ media
-Guinea pig inoculation
Modes of transmission
Inhalation , Ingestion, Inoculation , Transplacental
Route Spread
Local , Lymphatic , Haematogenous , By natural passages,
Pathogenesis
- Anti‐mycobacterial CMI, confers resistance to bacteria → dev. of HS to tubercular Ag
- Bacilli enters macrophages
- Replicates in phagosomeby blocking fusion of phagosome& lysosome, continues for 3 weeks →bacteremiabut asymptomatic
- After 3 wks, T helper response is mounted by IL‐12 produced by macrophages
- T cells produce IFN, activates macrophages → bactericidal activity, structural changes
- Macrophages secrete TNF→ macrophage recruitment, granuloma& necrosis
Fate of granuloma
- Caseousmaterial undergo liquefaction---cold abscess
- Bones, joints, lymph nodes & epididymis---sinuses are formed & sinus tract lined by tuberculousgranulation tissue
- Dystrophic calcification
Types of TB
1. Primary Pulmonary TB
2. secondary TB (miliary, fibrocaseous, cavitary)
3. Extra-pulmonary TB (bone, joints, renal, adrenal, skin… )
Primary TB
Infection in an individual who has not been previously infected or immunised
Primary complex
Sites
-lungs, hilarlymph nodes
-tonsils, cervical lymph nodes
-small intestine, mesenteric lymph nodes
Primary TB
In the lung, Ghon’scomplex has 3 components:
1. Pulmonary component -Inhalation of airborne droplet ~ 3 microns.
-Bacilli locate in the subpleuralmid zone of lung
-Brief acute inflammation –neutrophils.
-5-6 days-invoke granulomaformation.
-2 to 8 weeks –healing –single round ;1-1.5 cm-Ghon focus.
2. Lymphatic vessel component
3. Lymph node component
Fate of primary tuberculosis
- Lesions heal by fibrosis, may undergo calcification, ossification
-a few viable bacilli may remain in these areas
-bacteria goes into a dormant state, as long as the person's immune system remains active
- Progressive primary tuberculosis: primary focus continues to grow & caseousmaterial disseminated to other parts of lung
- Primary miliarytuberculosis: bacilli may enter circulation through erosion of blood vessel
- Progressive secondary tuberculosis: healed lesions are reactivated, in children & in lower resistance
Secondary tuberculosis
-Post-primary/ reinfection/ chronic TB
-Occurs in immunized individuals.
-Infection acquired from
-endogenous source/ reactivation
-exogenous source/ reinfection
Reactivation
-when immune system is depressed
-Common in low prevalence areas.
-Occurs in 10-15% of patients
-Slowly progressive (several months)
Re-infection
-when large innoculum of bacteria occurs
-In areas with increased personal contact
Secondary TB
-Sites-Lungs 1-2 cm apical consolidation with caseation
-Other sites -tonsils, pharynx, larynx, small intestine & skin
Fate of secondary tuberculosis
•Heal with fibrous scarring & calcification
•Progressive secondary pulmonary tuberculosis:
-fibrocaseoustuberculosis
-tuberculouscaseouspneumonia
-miliarytuberculosis
Complications:
a) aneurysm of arteries–hemoptysis
b) bronchopleuralfistula
c) tuberculousempyema
MiliaryTB
• Millet like, yellowish, firm areas without caseation
• Extensive spread through lympho-hematogenousroute
• Low immunity
• Pulmonary involvement via pulmonary artery
• Systemic through pulmonary vein:
-LN: scrofula, most common
-kidney, spleen, adrenal, brain, bone marrow
Signs and Symptoms of Active TB
• Pulmonary-cough, hemoptysis, dyspnea
• Systemic:
• fever
• night sweats
• loss of appetite
• weight loss
• chest pain,fatigue
•If symptoms persist for at least 2 weeks, evaluate for possible TB infection
Diagnosis
•Sputum-Ziehl Neelsen stain –10,000 bacilli, 60% sensitivity
-release of acid-fast bacilli from cavities intermittent.
-3 negative smears : low infectivity
•Culture most sensitive and specific test.
-Conventional Lowenstein Jensen media-10 wks.
-Liquid culture: 2 weeks
•Automated techniques within days
should only be performed by experienced laboratories (10 bacilli)
•PPD for clinical activity / exposure sometime in life
•X-ray chest
•FNAC
PPD Tuberculin Testing
- Read after 72 hours.
- Indurationsize -5-10 mm
- Does not d/s b/w active and latent infection
- False +: atypical mycobacterium
- False -: malnutrition, HD, viral, overwhelming infection, immunosuppression
- BCG gives + result.
Tuberculosis Atypical mycobacteria
- Photochromogens---M.kansasii
- Scotochromogens---M.scrofulaceum
- Non-chromogens---M.avium-intracellulare
- Rapid growers---M.fortuitum, M.chelonei
5 patterns of disease
- Pulmonary—M.kansasii, M.avium-intracellulare
- Lymphadenitis----M.avium-intracellulare, M.scrofulaceum
- Ulcerated skin lesions----M.ulcerans, M.marinum
- Abscess----M.fortuitum, M.chelonei
- Bacteraemias----M.avium-intracellulare as in AIDS
Autoimmune(acquired) Haemolytic anaemia
Auto antibodies are usually Ig g type (may be Ig M or Ig A). They may or may not bind complement and may be active in warm or cold temperature They may be complete (agggIutinating) or incomplete. Haemolysis s may be intravascular due to destruction of the antibody coated cells by RE system.
Causes:
a. Idiopathic
b. Secondary to
o Drugs - Methyldopa, Mefanamic acid
o Disease like
-> Infections especially viral.
-> Autoimmune disease especially SLE.
-> Lymphomas and chronic lymphatic leukaemia.
-> Tumours.
Diagnosis : is based on
• Evidences of haemolytic anaemia.
• Demonstration of antibodies
- On red cell surface by direct Coomb’s test
- In serum by indirect Coomb’s test.
HYPERTENSIVE VASCULAR DISEASE
Malignant hypertension
A small percentage of HTN patients (5%) present with a rapidly rising blood pressure that, if untreated, leads to death within 1 to 2 years.
systolic pressures -> 200 mm Hg or diastolic pressures -> 120 mm Hg
Associated with renal failure and retinal hemorrhages
Most commonly is superimposed on preexisting benign hypertension
Hypertension (HTN) has the following complications
- stroke (CVD)
- multi-infarct dementia
- atherosclerotic coronary heart disease
- cardiac hypertrophy and heart failure (hypertensive heart disease)
- aortic dissection
- renal failure
Essential HTN Accounts for 90% to 95% of all cases
SecondaryHTN
Renal - > Acute glomerulonephritis Chronic renal disease
Endocrine - > Cushing syndrome, Hypothyroidism (myxedema) Hyperthyroidism (thyrotoxicosis) Pregnancy-induced (pre-eclampsia)
Cardiovascular - > Coarctation of aorta
Neurologic
Psychogenic, Increased intracranial pressure
PATHOGENESIS
most cases (95%) are idiopathic (essential hypertension)
Most of the remaining cases (secondary hypertension) are due to primary renal disease, renal artery narrowing
Gene defects in enzymes involved in aldosterone metabolism
Mutations in proteins that affect sodium resorption as in Liddle syndrome
Genetic factors - > familial clustering of hypertension
Environmental factors such as stress, obesity, smoking, physical inactivity, and high levels of salt consumption, modify the impact of genetic determinants
Morphology
HTN is associated with arteriolosclerosis (small arterial disease)
Two forms of small blood vessel disease are hypertension-related:
1- hyaline arteriolosclerosis
2- hyperplastic arteriolosclerosis
Hyaline arteriolosclerosis
Associated with benign hypertension.
-marked by homogeneous, pink hyaline thickening of the arteriolar walls, and luminal narrowing.
Hyperplastic arteriolosclerosis
It is more typical of severe hypertension.
- "onionskin," concentric, laminated thickening of arteriolar walls and luminal narrowing.
- The laminations consist of smooth muscle cells and thickened, reduplicated basement membrane.
DISORDERS OF BLOOD VESSEL HYPERREACTIVITY
Several disorders are characterized by inappropriate or exaggerated vasoconstriction of blood vessels:
1- Raynaud Phenomenon
2- Myocardial Vessel Vasospasm
Raynaud Phenomenon
- results from exaggerated vasoconstriction of arteries and arterioles in the extremities (the fingers and toes, but also sometimes the nose, earlobes, or lips).
-restricted blood flow induces paroxysmal pallor or cyanosis
- involved digits characteristically show "red-white-andblue" color changes from most proximal to most distal
Myocardial Vessel Vasospasm
Causes: 1- vasoactive mediators - > prolonged vascular contraction;
- endogenous (e.g., epinephrine released by pheochromocytomas) or exogenous (cocaine or phenylephrine).
2- Elevated thyroid hormone -> increase sensitivity of vessels to catecholamines
3- autoantibodies and T cells in scleroderma vascular instability and vasospasm.
4- extreme psychological stress (release of catecholamines)
Cardiac raynaud
When vasospasm of cardiac arterial or arteriolar bed is of sufficient duration (20 to 30 min ) myocardial infarction occurs
acute microscopic area of necrosis characterized by mycotic hypercontraction (contraction band necrosis)
subacute and chronic cases - > microscopic foci of granulation tissue or scar
Chronic lymphocytic leukaemia
Commoner in middle age. It starts insidiously and often runs a long chronic course
Features:
- Lymphnode enlargement.
- Anaemia (with haemolytic element).
- Moderate splenomegaly.
- Haemorrhagic tendency in late stages.
- Infection.
Blood picture:
- Anaemia with features of haemolytic anaemia
- Total leucocytic count of 50-100,OOO/cu.mm.
- Upto 90-95% cells are lymphocytes and prolymphocytes.
- Thrombocytopenia may be seen.
Bone marrow. Lymphocytic series cells-are seen. Cells of other series are reduced,