Monday, April 29, 2013

Disorders of water-electrolytes metabolism


I- Disorders of water-electrolytes metabolism 
1. Water balance 
 A. Water content and distribution 
    Intracellular fluid (ICF))
       The fluid within cells. 
    Extracellular fluid (ECF)
       The fluid outside the cells =  interstitial fluid + intravascular fluid. 

Body fluid:  water + solutes 
         Accounts for 60% of body weight?

Body fluid varies with age, sex and the amount of body fat:
age ↑  body fluid  
 Adult females have a lower proportion of body fluid than the males of same age 
 fat ↑  body fluid    
   

B. Water daily balance 

2. Electrolytes in Body fluid


 --Na+ requirement is about 4-6g/day; 
 --mainly gain from daily salt supplement; 
 --About 90% is eliminated in the urine.  

 -- Characteristics of renal Na+ excretion: 
      High intake high excretion,   
      Low intake low excretion, 
      No intake no excretion. 
 -- Plasma [Na+]: 130~150mmol/L

3. Osmotic pressure in the body fluid 

  • Osmotic pressure of a solution depends on the amount of dissolved molecules or ions. 
  •  Plasma osmotic pressure contains colloid osmotic pressure and crystal osmotic pressure. 

Osmosis and Osmotic Pressure
When a semi-permeable membrane (a membrane that allows solvent molecules to flow through but not the solute particles) separates two solutions of different concentrations, there will be a net flow of solvent molecules from the solution where its
concentration is lower to the solution where its concentration is higher. This phenomenon is called Osmosis and driving pressure is called as Osmotic pressure.

Osmotic pressure:
Crystal osmotic pressure is formed by a lot of
 small molecular weight materials, such as 
 electrolyte,Glucose, BUN and so on. 
Colloid osmotic pressure is formed by large
  molecular weight materials such as proteins. 

>Osmotic pressure of ECF is roughly equivalent to ICF.  
>Water moves from areas of low osmolatity to areas of high osmolatity. 
>Normal plasma osmotic pressure is 280~ 310 mOsm/L. 

Functions of electrolytes:
1.Maintaining the osmotic and acetic-alkali equilibrium.
2. Maintaining the resting membrane potential and    generating the active membrane potential. 
3. Taking part in metabolism and physiologic  action. 

Functions of body water:

  • It is essential to metabolism of the body.
  • It acts as a transport vehicle.
  • It is a good lubricant.
  • It is necessary for temperature regulation. 

4. Regulation of water-salt metabolism 
--Water balance is regulated primarily by antidiuretic hormone (ADH) and the perception of thirst; 
-- Sodium balance is regulated by aldosterone. 

Regulating mechanism 

  Thirst center

The regulation of ADH

The regulation of RAAS

II. Disorders of water-sodium metabolism 
  

Dehydration 
    An excessive loss of body fluid resulting from various causes is termed dehydration. 

1. Hypertonic dehydration 
(1) Concept: 
   The dehydration in which water loss is in excess of Na+ loss and remaining ECF of the body is hypertonic is termed hypertonic dehydration
Characteristics: 
  a. loss of water > loss of sodium; 
  b. plasma Na+ > 150mmol/L;  
  c. plasma osmotic pressure > 310mOsm/L. 

(2) Causes: 
 A: Decreased water intake: 
    a. Inability to drink or loss of thirst:

  • difficulty in swallowing: esophageal cancer
  • unconsciousness: coma
  • brain injury: impaired thirst sensation

    b. Unavailableness of water: 
        e.g. desert district: desert travelling ocean accident; war, et al.

 B: Increased water output: 
     Body fluid lose from: skin, lungs, GI, kidney
   a. skin and lungs: 
       e.g. profuse sweating, fever 
   b. GI tract:  gastrointestinal track (GI)
       e.g. diarrhea, vomiting 
   c. Kidneys: 
       e.g. DM:
              insipidus: central defect in ADH production or secration a renal insensitivity to ADH
(3) Effects on the body 
Clinical characteristics: 
    Obvious thirst; mainly intracellular dehydration; a few patients occur circulatory failure (shock) at early stage. 

A. Compensation process: 

B. Decompensation (Clinical Manifestations) 

Dehydration fever: 
   Serious dehydration may lead to increased body temperature due to decreased evaporation from skin and impaired temperature regulatory function. 
    
Degree of hypertonic dehydration 

Principles of treatment 
   A. To treat primary disease; 
   B. To supply water: 
    --drink water, 
    --transfuse 5% glucose first, then 0.9% NaCl. 

2. Hypotonic dehydration 
(1) Concept: 
   The dehydration in which sodium loss is in excess of  water loss and remaining ECF of the body is hypotonic is termed hypotonic dehydration. 
Characteristics: 
  a. loss of sodium > loss of water; 
  b. plasma Na+ < 130mmol/L;  
  c. plasma osmotic pressure < 280mOsm/L. 
(2) Causes: 
The most common cause: 
   fluid loss + replacement of water or intravenous 5% glucose only. 

 Body fluid lose from: 
    A: GI tract: e.g. vomiting, diarrhea. 
    B: skin: perfuse sweating, a large area of burn.         
 C. Kidneys: 
    a. Administer some diuretics for a long time:  
    b. Lack of aldosterone: e.g. Addison’s disease 
    c. Intrinsic renal disease: 
       e.g. acute renal failure 
      The conditions of a and b can cause excessive   renal lose of sodium. 
(3) Effects on the body 
Clinical characteristics: 
    Mainly extracellular dehydration; circulatory failure (shock) easily occurs at early stage. 

A. Compensation process: 

B. Decompensation (Clinical Manifestations)  

Degree of hypotonic dehydration    

Principles of treatment 
  A. To treat the causes of the disease; 
   B. Administer sodium solution, either orally 
        or intravenously. 

3. Isotonic dehydration 
(1) Concept: 
   The dehydration in which water loss is equal to sodium loss and remaining ECF of the body is isotonic is termed isotonic dehydration. 
Characteristics: 
  a. water and sodium lost proportionally; 
  b. plasma Na+ = 130-150mmol/L;  
  c. plasma osmotic pressure = 280-310mOsm/L. 
(2) Causes: 
   A. Acute serious vomiting or diarrhea: 
   B. Skin burn in a large area: 
   C. Draw a large amount of ascites: 
   D. Paralytic ileus: 
(3) Effects on the body 
A. Compensation process: 

B. Decompensation (Manifestations)  


Principles of treatment 
   A. To treat original disease; 
   B. Supply isotonic fluid. 



Distribution of body fluid in dehydration  

Monday, April 22, 2013

Hodgkin's vs Non-Hodgkin's lymphoma

Lymphoma (malignant lymphoma, ML)
Definition:
   Lymphoma is a group of cancers arising primarily from lymph nodes and/or extranodal lymphoid tissues, showing features of lymphocytes.

Classification 
Hodgkin’s lymphoma (HD)
non-Hodgkin’s lymphoma (NHL)

 Hodgkin’s lymphoma(HL)
 Introduction
1. Age:two peaks of incidence
young adult: 15-27 years of age about 50 years of age

Hodgkin Lymphoma

 LM
 2. Feature → Reed-Sternberg cells (R-S c)   
mixed with rich inflammatory background
(1)  R-S cell

  • 15-45 um in diameter
  • Binucleate or multiple nuclei, acidophilic nucleoli
  • Amphophilic  cytoplasm

R - S cell

 Mirror image cell
 R-S cell 
with symmetric binuclei


 Hodgkin cell single nucleus R-S cell 

Others (variants)
i) Lacunar cell:
folded, multilobate nuclei surrounded
by pale cytoplasm

 ii) Type L & H R-S cell 
(Popcorn cell):
     have twisted , multilobate nuclei    
     resembling  popcorn kernels
iii) Undifferentiated or  Pleomorphic   R-S c

Popcorn cell

(2) Background
 1) Inflammatory c infiltration
Main: lymphocyte
Others:   plasam cells, neutrophil, eosinophil , histocyte
2) Fibrosis

Histological classification
1.Nodular lymphocyte predominant
      Hodgkin’s lymphoma 
2. Classical Hodgkin’s lymphoma

Classical Hodgkin’s lymphoma
   Features:
1-R-S c and Hodgkin c
2-Background: lymphocyte Plasma C, neutrophil, eosinophil, histocyte

(1)Nodular sclerosis HL
(2) Lymphocyte-rich classical HL
(3) Mixed cellularity
(4) Lymphocyte depletion

 Nodular sclerosis HL
Age:Young woman, 
Common Site:
I)cervical LN
II)supraclavicular
III)mediastinal LN
Prognosis: excellent
Features:

  • The presence of a particular variant of R-S c lacunar cells
  • The collagen bands that divided LN into circumscribed nodules

Nodular sclerosis HL

Nodular sclerosis HL :Lacunar  cell

(2)Lymphocyte-rich classical HL

  1. Hodgkin c and mirror image c             
  2. Background :LC or histocyte

Lymphocyte-rich classical HL

(3) Mixed cellularity, MC:
  Most common  form of HL

  •  Plantiful typical R-S cell
  •  Background: LC, PlasmaC, Eosiphil C, histocyte, fibroblast
  •  Small areas of necrosis and fibrosis

Mixed   cellularity



CD30+
CD15
CD30
CD3
EBV: LMP-1

EBV: EBER
Fish: EMER

(4) Lymphocyte depletion, LD
i)LC  
ii)relative abundance 
iii)R-S cell
iv)pleomorphic variants
     
 Two morphologic forms
i) Diffuse fibrosis
-LC 
-amorphous  protein materials  reticular fiber 
-R-S cell, histocyte, LC:less

ii) Reticular variants
 rich in cell:

  • Highly anaplastic R-S c
  • A few typical R-S cell
  • Massive necrosis
  • Poorly prognosis

Reticular variants

 Pathological diagnosis
1. Dependent on the LN biopsy
     Diagnostic value      
-Typical R-S cell  --- HL
-Lacunar cell ---→ nodular sclerosis

2. Immunohistochemistry
help to diagnosis
BC: CD20 (+) --- nodular LC predominance
HL: CD15 , CD30 (+)

           Stage  of  HD



The Non- Hodgkin lymphomas 
   The non- Hodgkin lymphoma are solid tumours arising in the peripheral lymphoid tissue particularly of lymphnodes but also of the extranodal sites such as the oro- pharynx, the gut, skin and other sites.

1. two-third  ---    primary in LN
   one-third   ---   primary in    
extranodal organs and tissues such as digestive , respiratory tract,lung , skin , CNS 
2. Diagnosis:dependent on the biopsy of LN or related tissue pathological diagnosis
-Histological classification
-Immune phenotype of tumor c

3. Classification

Model of LC transformation 


Gross: 

  • The same as Hodgkin’s diseases but the mass is more soft and a few necrosis.
  • The normal architecture of lymph node have been destroyed partly or entirely.
  • Very numerous monotonous neoplastic cell flood in lymph node.
  • The neoplastic cell may be infiltrate to the capsule of node.

B-cell small lymphocytic 

Example of Non-Hodgkin’s lymphoma 

  1. Follicular lymphoma
  2. Diffuse large B-cell lymphoma
  3. Burkitt lymphoma
  4. Mycosis fungoides

 Follicular lymphoma
 Drive from germinal center BC
 The most common form in the US
  (20-45%)
 Less in China(10%) 
 Age:adult 
Pathological features
Nodular growth pattern
Tumor follicle: composed of
i)Centrocyte:irregular and cleaved nuclear, scant cytoplasm
ii)Centroblast:open nuclear chromatin,several nucleoli

 Diffuse large B-cell lymphoma

  • Centroblast lymphoma
  • B immunoblast lymphoma
  • Anaplastic large BC lymphoma
  • TC-rich/histocyte BC lymphoma
  • Plasmablast lymphoma

Pathological features

  • Relatively large cell:4-5 times the diameter  of small LC
  • A fair degree of  morphologic variation: centroblast , immunoblast
  • Cell morphology: round or oval nucleus,2-3  nucleoli, margination of  chromatin moderate cytoplasm
  • Diffuse pattern of growth



Diffuse large cell,centroblastic

Burkitt’s lymphoma

  • Brukitt’s lymphoma was described initially in Africa, where it is endemic in some parts, but it is also ocure sporadically in nonendemic area.
  • Rare cases have been recorded in European and North America.
  • This disorder is relationship of the Epstein-Barr viruses.
  • Both the African and non Africa cases are found largely in children or young adults. 
Presentation of disease:
The disease rarely arises in lymph nodes, but usually appears in the jaw or ovaries (retroperitoneal tissues in males) this disease grows extremely rapidly and spreads extensively, leading quickly to complication.

Histological appearance is typical and striking
   1. diffuse proliferation of lymphoblasts (B cell type) cell medium- sized and uniform, mitoses frequent.
   2. Scattering of macrophages containing debris desired from very rapid cell turnover contributing ‘starry sky’. These benign macrophage are diffusely distributed among the tumor cell. The macrophage often sounded by a clear space.
NOTE:   Leukemic transformation may occur, but is uncommon, these tumors respond well to aggressive chemotherapy and long remissions have been reported. However, in most cases a relapse occurs, and a majority of patients die with in 5 years.

Burkitt’s lymphoma,starry-sky

Burkitt’s lymphoma,mitoses

Mycosis fungoides
   Mycosis fungoides are uncommon lymphoid malignancies that are primary in the skin. It is infrequent T cell lymphomas. These disease usually affects males 40-60 years of age.
   Grossly: The lesions begin as poorly defined areas of eczema, followed by formation of plaques and ultimately of multiple nodules. The nodules often rapture and become ulcer.
 Histologically: 
  This disease is characterized by dermal infiltrates of atypical lymphoid cell that invade the epidermis. The neoplastic cell (mycosis cells) have deeply lobulated or cerebra-form nuclei. Immunology studies indicate the presence of T cell markers on mycosis cells.